Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.
A delta-4 C19 steroid that is produced not only in the TESTIS, but also in the OVARY and the ADRENAL CORTEX. Depending on the tissue type, androstenedione can serve as a precursor to TESTOSTERONE as well as ESTRONE and ESTRADIOL.
Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.
Derivatives of the steroid androstane having three double bonds at any site in any of the rings.
The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.
Tumors or cancer of the human BREAST.
An aromatase inhibitor that is used in the treatment of advanced BREAST CANCER.
A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.
An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from ANDROSTENEDIONE directly, or from TESTOSTERONE via ESTRADIOL. In humans, it is produced primarily by the cyclic ovaries, PLACENTA, and the ADIPOSE TISSUE of men and postmenopausal women.
Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)
One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.
Certain tumors that 1, arise in organs that are normally dependent on specific hormones and 2, are stimulated or caused to regress by manipulation of the endocrine environment.
Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.
Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.
The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.
Enlargement of the BREAST in the males, caused by an excess of ESTROGENS. Physiological gynecomastia is normally observed in NEWBORNS; ADOLESCENT; and AGING males.
The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life.
Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH).
An antineoplastic agent that is a derivative of progesterone and used to treat advanced breast cancer.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.
The gamete-producing glands, OVARY or TESTIS.
A class of enzymes that catalyzes the oxidation of 17-hydroxysteroids to 17-ketosteroids. EC 1.1.-.
The process in developing sex- or gender-specific tissue, organ, or function after SEX DETERMINATION PROCESSES have set the sex of the GONADS. Major areas of sex differentiation occur in the reproductive tract (GENITALIA) and the brain.
A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).
One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.
Substances that possess antiestrogenic actions but can also produce estrogenic effects as well. They act as complete or partial agonist or as antagonist. They can be either steroidal or nonsteroidal in structure.
A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
A cyclic nucleotide formed from CYTIDINE TRIPHOSPHATE by the action of cytidylate cyclase. It is a potential cyclic nucleotide intracellular mediator of signal transductions.
Development of female secondary SEX CHARACTERISTICS in the MALE. It is due to the effects of estrogenic metabolites of precursors from endogenous or exogenous sources, such as ADRENAL GLANDS or therapeutic drugs.
A transcription factor and member of the nuclear receptor family NR5 that is expressed throughout the adrenal and reproductive axes during development. It plays an important role in sexual differentiation, formation of primary steroidogenic tissues, and their functions in post-natal and adult life. It regulates the expression of key steroidogenic enzymes.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.
A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum.
The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.
Region of hypothalamus between the ANTERIOR COMMISSURE and OPTIC CHIASM.
An OOCYTE-containing structure in the cortex of the OVARY. The oocyte is enclosed by a layer of GRANULOSA CELLS providing a nourishing microenvironment (FOLLICULAR FLUID). The number and size of follicles vary depending on the age and reproductive state of the female. The growing follicles are divided into five stages: primary, secondary, tertiary, Graafian, and atretic. Follicular growth and steroidogenesis depend on the presence of GONADOTROPINS.
A potent androgenic metabolite of TESTOSTERONE. It is produced by the action of the enzyme 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE.
An oxidoreductase that catalyzes the conversion of 3-oxo-delta4 steroids into their corresponding 5alpha form. It plays an important role in the conversion of TESTOSTERONE into DIHYDROTESTOSTERONE and PROGESTERONE into DIHYDROPROGESTERONE.
A malignant metastatic form of trophoblastic tumors. Unlike the HYDATIDIFORM MOLE, choriocarcinoma contains no CHORIONIC VILLI but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (TROPHOBLASTS). It is characterized by the large amounts of CHORIONIC GONADOTROPIN produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin (CHORIOCARCINOMA, NON-GESTATIONAL).
A triazine herbicide.
Catalyze the oxidation of 3-hydroxysteroids to 3-ketosteroids.
Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.
A structurally diverse group of compounds distinguished from ESTROGENS by their ability to bind and activate ESTROGEN RECEPTORS but act as either an agonist or antagonist depending on the tissue type and hormonal milieu. They are classified as either first generation because they demonstrate estrogen agonist properties in the ENDOMETRIUM or second generation based on their patterns of tissue specificity. (Horm Res 1997;48:155-63)
The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.
A mitochondrial cytochrome P450 enzyme that catalyzes the side-chain cleavage of C27 cholesterol to C21 pregnenolone in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11A1 gene, catalyzes the breakage between C20 and C22 which is the initial and rate-limiting step in the biosynthesis of various gonadal and adrenal steroid hormones.
The fluid surrounding the OVUM and GRANULOSA CELLS in the Graafian follicle (OVARIAN FOLLICLE). The follicular fluid contains sex steroids, glycoprotein hormones, plasma proteins, mucopolysaccharides, and enzymes.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Animals and plants which have, as their normal mode of reproduction, both male and female sex organs in the same individual.
Luciferases from RENILLA that oxidizes certain LUMINESCENT AGENTS to cause emission of PHOTONS.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.
Steroid hormones produced by the GONADS. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include ESTRADIOL; PROGESTERONE; and TESTOSTERONE.
A plant genus of the family LILIACEAE with roots that contain VERATRUM ALKALOIDS used as emetics, parasiticides, antihypertensives. It is the main ingredient of Boicil.
In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Hormones produced in the testis.
Hormones that stimulate gonadal functions such as GAMETOGENESIS and sex steroid hormone production in the OVARY and the TESTIS. Major gonadotropins are glycoproteins produced primarily by the adenohypophysis (GONADOTROPINS, PITUITARY) and the placenta (CHORIONIC GONADOTROPIN). In some species, pituitary PROLACTIN and PLACENTAL LACTOGEN exert some luteotropic activities.
A selective triazine herbicide. Inhalation hazard is low and there are no apparent skin manifestations or other toxicity in humans. Acutely poisoned sheep and cattle may show muscular spasms, fasciculations, stiff gait, increased respiratory rates, adrenal degeneration, and congestion of the lungs, liver, and kidneys. (From The Merck Index, 11th ed)
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
Exogenous agents, synthetic and naturally occurring, which are capable of disrupting the functions of the ENDOCRINE SYSTEM including the maintenance of HOMEOSTASIS and the regulation of developmental processes. Endocrine disruptors are compounds that can mimic HORMONES, or enhance or block the binding of hormones to their receptors, or otherwise lead to activating or inhibiting the endocrine signaling pathways and hormone metabolism.
Steroid-producing cells in the interstitial tissue of the TESTIS. They are under the regulation of PITUITARY HORMONES; LUTEINIZING HORMONE; or interstitial cell-stimulating hormone. TESTOSTERONE is the major androgen (ANDROGENS) produced.
Supporting cells projecting inward from the basement membrane of SEMINIFEROUS TUBULES. They surround and nourish the developing male germ cells and secrete ANDROGEN-BINDING PROTEIN and hormones such as ANTI-MULLERIAN HORMONE. The tight junctions of Sertoli cells with the SPERMATOGONIA and SPERMATOCYTES provide a BLOOD-TESTIS BARRIER.
Sexual activities of animals.
Gonadal interstitial or stromal cell neoplasm composed of only LEYDIG CELLS. These tumors may produce one or more of the steroid hormones such as ANDROGENS; ESTROGENS; and CORTICOSTEROIDS. Clinical symptoms include testicular swelling, GYNECOMASTIA, sexual precocity in children, or virilization (VIRILISM) in females.
Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction.
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
The flattened stroma cells forming a sheath or theca outside the basal lamina lining the mature OVARIAN FOLLICLE. Thecal interstitial or stromal cells are steroidogenic, and produce primarily ANDROGENS which serve as precusors of ESTROGENS in the GRANULOSA CELLS.
Those protein complexes or molecular sites on the surfaces of gonadal and other sensitive cells that bind gonadotropins and thereby modify the functions of those cells; hCG, LH, and FOLLICLE STIMULATING HORMONE are the major specific gonadotropins.
A cell line derived from cultured tumor cells.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The surgical removal of one or both ovaries.
Pain in the joint.
Development of male secondary SEX CHARACTERISTICS in the FEMALE. It is due to the effects of androgenic metabolites of precursors from endogenous or exogenous sources, such as ADRENAL GLANDS or therapeutic drugs.
The period of the MENSTRUAL CYCLE representing follicular growth, increase in ovarian estrogen (ESTROGENS) production, and epithelial proliferation of the ENDOMETRIUM. Follicular phase begins with the onset of MENSTRUATION and ends with OVULATION.
Those protein complexes or molecular sites on the surfaces and cytoplasm of gonadal cells that bind luteinizing or chorionic gonadotropic hormones and thereby cause the gonadal cells to synthesize and secrete sex steroids. The hormone-receptor complex is internalized from the plasma membrane and initiates steroid synthesis.
An order of bottom fishes with short, small, spinous dorsal fins. It is comprised of one family (Batrachoididae) and about 70 species.
Tumors or cancers of the ADRENAL CORTEX.
A genus of BIRDS in the family Phasianidae, order GALLIFORMES, containing the common European and other Old World QUAIL.
Pathological processes involving any part of the UTERUS.
The mechanisms by which the SEX of an individual's GONADS are fixed.
Enzymes that catalyze the oxidation of estradiol at the 17-hydroxyl group in the presence of NAD+ or NADP+ to yield estrone and NADH or NADPH. The 17-hydroxyl group can be in the alpha- or beta-configuration. EC
Large, long-tailed reptiles, including caimans, of the order Loricata.
Cell surface proteins that bind FOLLICLE STIMULATING HORMONE with high affinity and trigger intracellular changes influencing the behavior of cells.
Organometallic compounds which contain tin and three alkyl groups.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Megestrol acetate is a progestogen with actions and uses similar to those of the progestogens in general. It also has anti-androgenic properties. It is given by mouth in the palliative treatment or as an adjunct to other therapy in endometrial carcinoma and in breast cancer. Megestrol acetate has been approved to treat anorexia and cachexia. (From Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
The surgical removal of one or both testicles.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
The most diversified of all fish orders and the largest vertebrate order. It includes many of the commonly known fish such as porgies, croakers, sunfishes, dolphin fish, mackerels, TUNA, etc.
Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.
The mucous membrane lining of the uterine cavity that is hormonally responsive during the MENSTRUAL CYCLE and PREGNANCY. The endometrium undergoes cyclic changes that characterize MENSTRUATION. After successful FERTILIZATION, it serves to sustain the developing embryo.
An enzyme that catalyzes the reduction of TESTOSTERONE to 5-ALPHA DIHYDROTESTOSTERONE.
Fushi tarazu transcription factors were originally identified in DROSOPHILA. They are found throughout ARTHROPODS and play important roles in segmentation and CENTRAL NERVOUS SYSTEM development.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Common name for small PASSERIFORMES in the family Fringillidae. They have a short stout bill (BEAK) adapted for crushing SEEDS. Some species of Old World finches are called CANARIES.
Development of SEXUAL MATURATION in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of PUBERTY in the population. This early maturation of the hypothalamic-pituitary-gonadal axis results in sexual precocity, elevated serum levels of GONADOTROPINS and GONADAL STEROID HORMONES such as ESTRADIOL and TESTOSTERONE.
A species of baboon in the family CERCOPITHECIDAE with a somewhat different social structure than PAPIO HAMADRYAS. They inhabit several areas in Africa south of the Sahara.
Conditions of sexual ambiguity in which the individual possesses gonadal tissues of both sexes, tissues from the OVARY and the TESTIS. There can be a testis on one side and an ovary on the other (lateral), or there may be combined ovarian and testicular tissue (ovotestes) on each side (bilateral). The karyotype may be 46,XX; 46,XY; or a mosaic of 46,XX/46,XY. These disorders have historically been called true hermaphroditism.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Cytoplasmic proteins that bind estradiol, migrate to the nucleus, and regulate DNA transcription.
A family of freshwater fish comprising the minnows or CARPS.
The degeneration and resorption of an OVARIAN FOLLICLE before it reaches maturity and ruptures.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN).
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.
A monoamine oxidase inhibitor with antihypertensive properties.
The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the ENDOCRINE GLANDS, included are the CHROMAFFIN SYSTEM and the NEUROSECRETORY SYSTEMS.
The D-isomer of ASPARTIC ACID.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
A species of PERCIFORMES commonly used in saline aquaculture.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
A subclass of repressor proteins that do not directly bind DNA. Instead, co-repressors generally act via their interaction with DNA-BINDING PROTEINS such as a TRANSCRIPTIONAL SILENCING FACTORS or NUCLEAR RECEPTORS.
An estrogen responsive cell line derived from a patient with metastatic human breast ADENOCARCINOMA (at the Michigan Cancer Foundation.)
A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.
A malignant neoplasm of the ADRENAL CORTEX. Adrenocortical carcinomas are unencapsulated anaplastic (ANAPLASIA) masses sometimes exceeding 20 cm or 200 g. They are more likely to be functional than nonfunctional, and produce ADRENAL CORTEX HORMONES that may result in hypercortisolism (CUSHING SYNDROME); HYPERALDOSTERONISM; and/or VIRILISM.
Sexual union of a male and a female in non-human species.
Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.
A major gonadotropin secreted by the human adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and the LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. The alpha subunit is common in the three human pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
A neoplasm composed entirely of GRANULOSA CELLS, occurring mostly in the OVARY. In the adult form, it may contain some THECA CELLS. This tumor often produces ESTRADIOL and INHIBIN. The excess estrogen exposure can lead to other malignancies in women and PRECOCIOUS PUBERTY in girls. In rare cases, granulosa cell tumors have been identified in the TESTES.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Phospholipoglycoproteins produced in the fat body of egg-laying animals such as non-mammalian VERTEBRATES; ARTHROPODS; and others. Vitellogenins are secreted into the HEMOLYMPH, and taken into the OOCYTES by receptor-mediated ENDOCYTOSIS to form the major yolk proteins, VITELLINS. Vitellogenin production is under the regulation of steroid hormones, such as ESTRADIOL and JUVENILE HORMONES in insects.
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.
Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.
Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The inferior and superior venae cavae.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Hormones produced by the GONADS, including both steroid and peptide hormones. The major steroid hormones include ESTRADIOL and PROGESTERONE from the OVARY, and TESTOSTERONE from the TESTIS. The major peptide hormones include ACTIVINS and INHIBINS.
A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)
A metabolite of PROGESTERONE with a hydroxyl group at the 17-alpha position. It serves as an intermediate in the biosynthesis of HYDROCORTISONE and GONADAL STEROID HORMONES.
A sudden, temporary sensation of heat predominantly experienced by some women during MENOPAUSE. (Random House Unabridged Dictionary, 2d ed)
Glycoproteins that inhibit pituitary FOLLICLE STIMULATING HORMONE secretion. Inhibins are secreted by the Sertoli cells of the testes, the granulosa cells of the ovarian follicles, the placenta, and other tissues. Inhibins and ACTIVINS are modulators of FOLLICLE STIMULATING HORMONE secretions; both groups belong to the TGF-beta superfamily, as the TRANSFORMING GROWTH FACTOR BETA. Inhibins consist of a disulfide-linked heterodimer with a unique alpha linked to either a beta A or a beta B subunit to form inhibin A or inhibin B, respectively
PLANT EXTRACTS and compounds, primarily ISOFLAVONES, that mimic or modulate endogenous estrogens, usually by binding to ESTROGEN RECEPTORS.

Constitutional genetic variation at the human aromatase gene (Cyp19) and breast cancer risk. (1/1297)

The activity of the aromatase enzyme, which converts androgens into oestrogens and has a major role in regulating oestrogen levels in the breast, is thought to be a contributing factor in the development of breast cancer. We undertook this study to assess the role of constitutional genetic variation in the human aromatase gene (Cyp19) in the development of this disease. Our genotyping of 348 cases with breast cancer and 145 controls (all Caucasian women) for a published tetranucleotide repeat polymorphism at intron 4 of the Cyp19 gene revealed the presence of six common and two rare alleles. Contingency table analysis revealed a significant difference in allelic distribution between cases and controls (chi2 5df = 13.52, P = 0.019). The allele measuring 171 bp was over-represented in cases; of 14 individuals homozygous for this allele, 13 were cases. These individuals had a higher incidence of cancer in family members and an earlier age at diagnosis than other cases. In sequencing Cyp19's coding exons and regulatory regions, we discovered a perfect association between a silent polymorphism (G-->A at Val80) and the high-risk genotype. Our conclusion is that constitutional genetic variation at the Cyp19 locus is associated with the risk of developing breast cancer, with the 171-bp allele serving as the high-risk allele.  (+info)

Endometriosis: a dysfunction and disease of the archimetra. (2/1297)

Endometriosis is considered primarily a disease of the endometrial-subendometrial unit or archimetra. The clinical picture of endometriosis characterises this disease as a hyperactivation of genuine archimetrial functions such as proliferation, inflammatory defence and peristalsis. While the aetiology of the disease remains to be elucidated, a key event appears to consist in the local production of extraovarian oestrogen by a pathological expression of the P450 aromatase. The starting event may consist in a hyperactivity of the endometrial inflammatory defence, a hyperactivity of the endometrial oxytocin/oxytocin receptor system or in the pathological expression of the P450 aromatase system itself. Regardless of which of these levels the starting event is localized in, they influence each other on both the level of the archimetra and the endometriotic lesions. Locally elevated oestrogen levels inevitably up-regulate the endometrial oxytocin mRNA and increased levels of oxytocin result in uterine hyperperistalsis, increased transtubal seeding of endometrial tissue fragments and finally subfertility and infertility by impairment of the uterine mechanism of rapid and sustained sperm transport. Locally increased levels of oestrogen lead, on both the level of the endometrial-subendometrial unit and the endometriotic lesion, to processes of hyperproliferation. These processes result, on the level of the uterus, in an infiltrative growth of elements of the archimetra into the neometra and, on the level of the endometriotic lesion, in infiltrative endometriosis. There is circumstantial evidence that trauma might be an important initial event that induces the specific biochemical and cellular responses of the archimetra. This model is able to explain both the pleiomorphic appearance of endometriosis and the, up until now, enigmatic infertility associated with mild and moderate endometriosis.  (+info)

The aromatase inactivator 4-hydroxyandrostenedione (4-OH-A) inhibits tamoxifen metabolism by rat hepatic cytochrome P-450 3A: potential for drug-drug interaction of tamoxifen and 4-OH-A in combined anti-breast cancer therapy. (3/1297)

Tamoxifen (tam), an anti-breast cancer agent, is metabolized into tam-N-oxide by the hepatic flavin-containing monooxygenase and into N-desmethyl- and 4-hydroxy-tam by cytochrome P-450s (CYPs). Additionally, tam is metabolically activated by hepatic CYP3A, forming a reactive intermediate that binds covalently to proteins. Tam and 4-hydroxyandrostenedione (4-OH-A) are currently used to treat breast cancer, and it has been contemplated that 4-OH-A be given concurrently with tam to contravene potential tumor resistance to tam. Because alterations in tam metabolism may influence its therapeutic efficacy, the effect of 4-OH-A on tam metabolism was examined. Incubation of tam with liver microsomes from phenobarbital-treated rats, in the presence of 4-OH-A (10-100 microM), resulted in marked inhibition of tam-N-demethylation and tam covalent binding and in decreased tam-N-oxide accumulation; however, there was no inhibition of the formation of 4-hydroxy-tam and of 3,4-dihydroxytamoxifen. These findings indicate that 4-OH-A inhibits CYP3A, but not P-450(s) that catalyze tam 4-hydroxylation. The diminished tam-N-oxide accumulation could be due to decreased N-oxide formation and/or due to increased N-oxide reduction. Incubation of tam-N-oxide with liver microsomes containing heat-inactivated flavin-containing monooxygenase demonstrated that 4-OH-A increases the accumulation of tam, possibly by diminishing its P-450-mediated metabolism. Kinetic studies indicate that 4-OH-A is a competitive inhibitor of CYP3A, but not a time-dependent inactivator. Consequently, the concurrent treatment of tam and 4-OH-A may result in increased tam half-life and thus could potentiate the therapeutic efficacy of tam and diminish the potential side effects of tam by inhibiting its covalent binding to proteins and possibly to DNA.  (+info)

The mechanism of action of epidermal growth factor and transforming growth factor alpha on aromatase activity in granulosa cells from polycystic ovaries. (4/1297)

We investigated aromatization and the mechanism of action of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) on oestradiol biosynthesis in freshly prepared granulosa cells from polycystic ovaries. Freshly prepared granulosa cells from polycystic ovaries incubated for only 3 h under basal conditions secreted significantly (P< 0.001) greater amounts of oestradiol-17beta than that of granulosa cells from normal ovaries. 8-Bromo-cyclic adenosine monophosphate (8-Br-cAMP), but not follicle stimulating hormone (FSH) or luteinizing hormone (LH), further enhanced this activity. Both EGF and TGFalpha inhibited gonadotrophinor 8-Br-cAMP-stimulated, but not basal, oestradiol production. LH receptor (LHR) binding, estimated by immunolabelling the bound LH, was significantly (P< 0.001) reduced in granulosa cells from polycystic ovaries when compared with cells from normal ovaries. EGF or TGFalpha significantly reduced the binding in cultured cells from all patient groups (P< 0.05). More interestingly, a further increase of the inhibitory effect was seen in granulosa cells from polycystic ovaries (P < 0.001). In conclusion, granulosa cells from polycystic ovaries contain high levels of basal aromatase activity in vitro, which is probably inherited from the in-vivo condition. EGF and TGFalpha suppress oestradiol synthesis at a step beyond the production of cAMP and also LHR binding with more effect in granulosa cells from polycystic ovaries.  (+info)

Effect of labor induction on the expression of oxytocin receptor, cytochrome P450 aromatase, and estradiol receptor in the reproductive tract of the late-pregnant ewe. (5/1297)

In this study, we investigated the timing of changes in aromatase, estradiol receptor, and oxytocin receptor expression in ovine uterine and placental tissues before parturition. Labor was induced by betamethasone injection into the fetus on Days 130-132 of pregnancy. Tissue samples were collected at injection and then every 14 h until labor (56 h) from four ewes at each time point. Samples were analyzed for aromatase, estradiol receptor, and oxytocin receptor expression by in situ hybridization; for oxytocin binding to its receptor using a specific antagonist; and for estradiol receptor quantitation by immunocytochemistry. Aromatase mRNA expression increased by 14 h postinjection (p < 0.02) in the fetal villi and remained high until labor. Expression of estradiol and oxytocin receptor mRNAs was unchanged in myometrium but increased in the endometrial luminal epithelium by 28 h (p < 0.05) and remained high until labor. Estradiol receptor protein concentration increased modestly at labor while oxytocin receptor binding in the luminal epithelium changed in parallel to the mRNA concentration. IN CONCLUSION: 1) induction of aromatase may facilitate the expression of endometrial estradiol and oxytocin receptors in the placentome, 2) changes in endometrial rather than myometrial oxytocin receptor may be important in inducing parturition, and 3) the transcription of estradiol receptor and oxytocin receptor in the uterine epithelium are positively correlated during parturition.  (+info)

A 500-bp region, approximately 40 kb upstream of the human CYP19 (aromatase) gene, mediates placenta-specific expression in transgenic mice. (6/1297)

In humans, aromatase P450 (product of CYP19 gene), which catalyzes conversion of C19 steroids to estrogens, is expressed in a number of tissues, including ovary, adipose, and syncytiotrophoblast of the placenta. The 5' untranslated regions of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are spliced onto a common site just upstream of the translation initiation site in exon II. In placenta, the 5' untranslated region of CYP19 mRNA transcripts is encoded by exon I.1, which lies approximately 40 kb upstream of exon II. To map genomic sequences required for placenta-specific CYP19 expression, fusion genes containing 2,400 and 501 bp of placenta-specific exon I.1 5' flanking DNA linked to the human growth hormone gene (hGH), as reporter, were introduced into transgenic mice. Expression of CYP19(I.1):hGH fusion genes containing as little as 501 bp of 5' flanking DNA was placenta-specific and developmentally regulated. Furthermore, transgene expression occurred specifically in the labyrinthine trophoblast of the mouse placenta, which contains syncytial cells that may be analogous to the human syncytiotrophoblast. We show that a relatively small segment of DNA (approximately 500 bp) >40 kb upstream of the protein coding region of a human gene is able to direct expression in an appropriate tissue- and cell-specific manner in transgenic mice. These findings suggest that 5' flanking DNA within 501 bp of exon I.1 of the human CYP19 gene contains cis-acting elements that bind placenta-specific transcription factors that are conserved between humans and mice.  (+info)

Intrafollicular content of luteinizing hormone receptor, alpha-inhibin, and aromatase in relation to follicular growth, estrous cycle stage, and oocyte competence for in vitro maturation in the mare. (7/1297)

The intrafollicular content of LH receptor, alpha-inhibin, and aromatase are known good indicators of follicular status. We investigated the amounts of these proteins in granulosa and cumulus cells in relation to oocyte competence for in vitro maturation, follicular growth, and estrous cycle stage in the mare. Follicular punctures were performed 34 h after an injection of crude equine gonadotropins, either during the follicular phase, at the end of the follicular phase, or during the luteal phase. The cumulus-oocyte complex, granulosa cells, and follicular fluid of follicles larger than 5 mm were collected. The nuclear stage of the oocytes after in vitro culture was determined microscopically. Granulosa and cumulus cell amounts of LH receptor, alpha-inhibin, and aromatase were assessed by the semiquantitative Western blot method and image analysis. Follicular fluids were assayed for progesterone (P4) and estradiol-17beta (E2). The three factors were expressed in mural granulosa and cumulus cells from all follicles from the gonadotropin-independent growth period until the preovulatory stage. Considering all the follicles punctured, the amounts of LH receptor and alpha-inhibin in granulosa cells were not different for the three physiological stages studied. The amounts of aromatase in granulosa cells, as well as the E2:P4 ratios, were higher for follicles punctured during the follicular phase than for the two other groups (p < 0.05). Considering the data from the three groups, the E2:P4 ratio and the LH receptor and aromatase contents, but not alpha-inhibin, in granulosa cells increased with an increase in follicular diameter (p < 0.01). The E2:P4 ratios and the amounts of LH receptor, alpha-inhibin, and aromatase in granulosa cells were lower in follicles 5-9 mm in diameter than in larger ones (p < 0.05). In cumulus cells, the amounts of the three factors were different neither between the three groups nor between the follicular diameters. Although we could not establish any obvious relationship to oocyte competence for in vitro maturation, the influence of the follicle diameter on the content of LH receptors, alpha-inhibin, and aromatase in granulosa cells was similar to the influence of follicle diameter on oocyte competence. Therefore, one can hypothesize that, in the mare, there is a link between the acquisition of oocyte competence and the expression of these factors in the follicular cells.  (+info)

Dynamics of periovulatory steroidogenesis in the rhesus monkey follicle after ovarian stimulation. (8/1297)

The temporal relationships and regulation of events in the primate follicle during the periovulatory interval are poorly understood. This study was designed to elucidate the dynamics of steroid synthesis in the macaque follicle during ovarian stimulation cycles in which serum/follicular fluid aspirates were collected at precise intervals before (0 h) and after (up to 36 h) administration of the ovulatory human chorionic gonadotrophin (HCG) bolus. Serum concentrations of progesterone increased (P < 0.05) within 30 min, and follicular fluid progesterone concentrations were elevated 180-fold within 12 h, of HCG injection, and remained elevated until the time of ovulation. In contrast, 17beta-oestradiol concentrations increased initially, but then declined (P < 0.05) by 36 h post-HCG. Acute incubation of granulosa cells with and without steroidogenic substrates demonstrated that: (i) 3beta-hydroxysteroid dehydrogenase and aromatase activities were present in equivalent amounts before and after HCG; whereas (ii) P450 side-chain cleavage activity increased (P < 0.05) within 12 h of HCG; and (iii) exogenous low-density lipoprotein and cholesterol were not utilized for steroidogenesis. This model should be useful for further studies on ovulation and luteinization in primates, and enable elucidation of the local actions of progesterone and other steroids at specific time points during the periovulatory interval.  (+info)

Fingerprint Dive into the research topics of Immunohistochemical localization of aromatase cytochrome P-450 and estradiol dehydrogenase in the syncytiotrophoblast of the human placenta. Together they form a unique fingerprint. ...
Aromatase cytochrome P450, the key enzyme of estrogen biosynthesis from androgens, is encoded by CYP19. Its structure shows some peculiarities: exons II to X encode the protein, while multiple alternative exons I encode unique 5-untranslated regions of the aromatase mRNA transcripts. Immunohistochemistry studies in the rat have shown that pituitary aromatase expression is sex-dependent and varies across the estrous cycle, suggesting that estrogens might be involved in the regulation of aromatase activity and might act locally as a paracrine or autocrine factor in the pituitary. In the present study, we used RT-PCR to characterize aromatase transcripts and real-time PCR to quantify the expression of the total aromatase mRNA at the different stages of the estrous cycle and from an ovariectomy and estradiol replacement model. We identified the two previously described aromatase transcripts with a specific 5untranslated region of the brain 1f and the gonadal PII transcripts. Total aromatase mRNA
TY - JOUR. T1 - Aromatase P450 gene expression in human adipose tissue. T2 - Role of a Jak/STAT pathway in regulation of the adipose-specific promoter. AU - Zhao, Ying. AU - Nichols, John E.. AU - Bulun, Serdar E.. AU - Mendelson, Carole R.. AU - Simpson, Evan R.. PY - 1995/7/7. Y1 - 1995/7/7. N2 - In the present report we describe a heretofore unrecognized role for a Jak/STAT signaling pathway, namely the stimulation of expression of the aromatase P450 (CYP19) gene, and hence of estrogen biosynthesis, in human adipose tissue. Expression of this gene in adipose tissue as well as in adipose stromal cells maintained in the presence of serum and glucocorticoids is regulated by a distal TATA-less promoter, I.4, which contains a glucocorticoid response element, an Sp1 binding site, and an interferon-γ activation site (GAS) element. The stimulatory action of serum (in the presence of dexamethasone) can be replaced by interleukin (IL)-11, leukemia inhibitory factor, and oncostatin-M, as well as by ...
Objective To observe the effect of transcutaneuos acupoint electrostimulation(TAES)on ovarian serum sex hormone levels and ovarian follicle granular cell aromatase cytochrome P 450(P 450arom)protein and follicle theca cell cytochrome P 450 17α-hydroxylase/c 17-20 lyase cytochrome P 450(P 450c17α)protein expression in polycystic ovary syndrome(PCOS)rats,so as to explore its mechanisms underlying improvement of PCOS.Methods Forty SD rats were randomly divided into four groups:normal control,model,medication and TAES(10rats/group).The PCOS model was established by giving(gavage)the animals with letrozole solution(1.0mg/kg,once daily for 21 consecutive days).Rats of the medication group were treated with Clomiphene(1mg/kg)once daily for 7days,and those of the TAES group were treated with electrical stimulation(2Hz,3mA)ofGuanyuan(CV 4)andSanyinjiao(SP 6)areas for 30 min,once daily for 7consecutive days.The rats body weight and bilateral ovarian weight were detected,and the ovarian structure and ...
Estrogen production within the testis has been a subject of substantial interest for years. Testicular germ cells and epididymal sperm have been hypothesized to be capable of synthesizing active P450 aromatase (P450arom), the estrogen synthesizing enzyme. This investigation was undertaken to establish that testicular germ cells and epididymal sperm contain active P450arom, to determine if P450arom mRNA is synthesized in germ cells, and to examine if there is a difference in the transcription of the P450arom gene between male germ cells and somatic cells. Specifically, the objectives of this research were: (1) to determine if adult mouse epididymal sperm contain active P450arom; (2) to determine if adult rat testicular germ cells and epididymal sperm contain active P450arom; (3) to determine if P450arom mRNA is expressed in adult rat germ cells; and (4) to determine if differences exist between germ cell and somatic cell P450arom transcripts. The major findings were: (1) adult mouse epididymal ...
Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine-POEA and alkyl polyglucoside-APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH
Specifically, qRT-PCR analysis of gene expression in living zebrafish embryos was applied to detect and characterize the effects of: (1) EDCs that act via ERs to induce brain P450 aromatase (P450aromB) and hepatic vitellogenin (vtg) expression; (2) EDCs that act via AhRs to reduce gonadal aromatase (P450aromA) and increase hepatic P4501A1 expression; (3) EDCs that interact directly with preformed aromatase enzymes to block aromatization; and (4) EDCs that perturb ER and AhR expression.. Primer Design and Optimization of qRT-PCR Conditions. P450aromB and -A. Assay development and validation in embryonic, larval, and adult male and female zebrafish has been completed (Sawyer and Callard, in preparation, 2004). Results show that the assay is sensitive and precise (linear between 1 x 10-6 and 1.0 ng mRNA). Reproducibility is excellent within and across operators when tested in multiple experiments and at multiple starting points within a single experiment (e.g., RNA extraction, RT, PCR)(intra- and ...
While several studies have addressed ER and AR expression in the brain of teleosts [16-20], virtually nothing is known about its sex differences, with only one study investigating AR expression levels in the whole brain of wrasse [21]. In the present study, we demonstrated that ER and AR are, to a large extent, differentially expressed between the sexes in the medaka brain. In teleosts, circulating testosterone levels in females are substantial and are sometimes equal to the levels found in males; females undergo a large preovulatory surge of circulating testosterone [22]. Meanwhile, brain aromatase activity in teleosts is 100-1000 times greater than in mammals and birds, resulting in a high amount of oestrogen even in the male brain [23]. Considering these facts, sex differences in the sex steroid milieu in the teleost brain are likely to be smaller compared with other vertebrates. Our present observation of the marked sexual dimorphism in neural ER and AR expression suggests that sex ...
Nathalie Hinfray, Edith Chadili, Benjamin Piccini, Morgane Caulier, Jean-Marc Porcher, et al.. Dynamic and differential expression of the gonadal aromatase during the process of sexual differentiation in novel transgenic cyp19a1a-GFP zebrafish line. 8. International symposium on fish endocrinology (8 ISFE), Jun 2016, Gothenburg, Sweden. pp.54. ⟨ineris-01853054⟩ ...
Over the past two decades, the female hormone 17β-estradiol (estrogen) has emerged as an important contributor to energy homeostasis in both males and females. Early clinical evidence involved the observation that men lacking estrogen synthesis secondary to mutations in aromatase-the enzyme that converts androgen to estrogen-or men harboring estrogen resistance secondary to mutation of the estrogen receptor (ER)α, develop visceral obesity, insulin resistance, and/or glucose intolerance (1,2). As an experimental confirmation, it was observed that elimination of the aromatase or ERα genes in male and female mice produced the same metabolic syndrome as in humans (3,4). Thus, it is reasonable to assume that although men have lower circulating estrogen concentrations than premenopausal women, aromatization of circulating androgen to estrogen in target metabolic tissues equilibrates cellular estrogen concentrations, and ER activation is critical in both sexes in promoting fuel homeostasis (5). This ...
Nathalie Hinfray, Elisabeth Pellegrini, Olivier Kah, Jean-Marc Porcher, Farzad Pakdel, et al.. Brain and gonadal aromatase as potential targets for endocrine disrupting chemicals (EDCS) in a model species, the zebrafish (Danio rerio). 12. International Symposium on toxicity assessment, Jun 2005, Skiathos, Greece. ⟨ineris-00969995⟩ ...
Aromatase plays a key role in sex differentiation of gonads. In this study, we cloned the full-length cDNA of ovarian aromatase from protogynous hermaphrodite red-spotted grouper (Epinephelus akaara), and prepared the corresponding anti-EaCyp19a1a antiserum. Western blot and immunofluorescence studies revealed ovary-specific expression pattern of EaCyp19a1a in adults and its dynamic expression change during artificial sex reversal. EaCyp19a1a was expressed by follicular cells of follicular layer around oocytes because strong EaCyp19a1a immunofluorescence was observed in the cells of ovaries. During artificial sex reversal, EaCyp19a1a expression dropped significantly from female to male, and almost no any positive EaCyp19a1a signal was observed in testicular tissues. Then, we cloned and sequenced a total of 1967 bp T-flanking sequence of EaCyp19a1a promoter, and showed a number of potential binding sites for some transcriptional factors, such as SOX5, GATA gene family, CREB, AP1, FOXL1, C/EBP, ...
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Article Impairments in aromatase expression, reproductive behavior, and sperm quality of male fish exposed to 17β‐estradiol. Growing evidence shows that environmental estrogen can reach levels that are high enough to exert adverse reproductive effect...
victor: The smell of women caused by aromatase. In their ovulation period, the estrogen level is the highest, in that time aromatase is plenty, because it is needed to convert androgen (testosteron) to estrogen. Their smell can be caused of that. BUT, it could be from something else, because in the period, women producing more sweat and (sorry) the blood things. If they dont clean their body well, so they produce bad smell. This is hygiene stuff ...
As someone working with a lot of women with oestrogen-dependent conditions, such as fibroids, endometriosis, cysts etc., I have always noticed the high incidence of gut inflammation in these patients. Often reducing inflammation in the gut, and systemically throughout the body, can help to significantly reduce or get rid of many of the symptoms typical for these conditions. Absorption of nutrients will undoubtedly play a big part in this, but there are some other, more direct mechanisms to do with inflammation that are becoming more apparent these days. One of the mechanisms responsible for this improvement is that by reducing inflammation one can reduce oestrogen levels - here is the mechanism explained ... Inflammatory agents have an effect on aromatase conversion. Aromatase is an enzyme that promotes the conversion of testosterone into oestrogen, so once activated more oestrogen is produced. ...
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The pituitary gland is part of hypothalamic-pituitary-gonadal axis, which controls development, reproduction, and aging in humans and animals. In addition, the pituitary gland is regulated mainly by hormones and neurotransmitters released from the hypothalamus and by systemic hormones secreted by target glands. Aromatase P450, the enzyme responsible for the catabolization of aromatizable androgens to estrogens, is expressed in different parts of body, including the pituitary gland. Moreover, aromatase P450 is involved in sexual dimorphism where alteration in the level of aromatase can initiate a number of diseases in both genders. On the other hand, the direct actions of estrogens, mainly estradiol, are well known for stimulating prolactin release. Numerous studies have shown that changes in the levels of estrogens, among other factors, have been implicated in the genesis and development of prolactinoma. The pituitary gland can produce estradiol locally in several types of endocrine cells, and it is
The molecular mechanisms involved in adrenocortical tumorigenesis are still not completely understood. In this study, using the H295R cell line as a model system, we investigated the role of estrogens and estrogen receptor (ER) alpha and ER beta in the growth regulation of adrenocortical tumors. We demonstrated that H295R cells are able to convert androgens to estrogens by a constitutive expression of active cytochrome P450 aromatase protein and express ER beta to a greater extent than ER alpha. Moreover, physiological concentrations of 17beta-estradiol (E2) determined an increase of thymidine incorporation, suggesting the presence of an autocrine mechanism in maintaining H295R cell proliferation. Evaluating the response to ER antagonists like 4-hydroxytamoxifen (OHT) and ICI 182 780 (ICI), we observed an up-regulation of ER beta and a dose-dependent inhibition of H295R cell proliferation. Whereas ICI determined the growth arrest of H295R cells, OHT induced morphological changes that were ...
TY - JOUR. T1 - Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase. AU - Seto-Young, D.. AU - Avtanski, D.. AU - Parikh, G.. AU - Suwandhi, P.. AU - Strizhevsky, M.. AU - Araki, T.. AU - Rosenwaks, Z.. AU - Poretsky, L.. PY - 2011/2/16. Y1 - 2011/2/16. N2 - The effects of rosiglitazone or pioglitazone (thiazolidinediones, TZDs) on estrogen production and aromatase activity in human ovarian cells were examined. Human granulosa cells were incubated in the tissue culture medium supplemented with androstenedione or testosterone, with or without insulin, TZDs, or type 1 17-hydroxysteroid-dehydrogenase (17-HSD) inhibitor. Estrogen concentrations in the conditioned medium, aromatase mRNA and protein expression in the cells and androgen substrate binding to aromatase were measured. With androstenedione as substrate, rosiglitazone or pioglitazone inhibited estrone production by up to 22% (p,0.012) while type 1 17-HSD ...
Gonçalves D, Saraiva JL, Teles M, Teodósio R, Canario AVM, Oliveira RF. Brain aromatase mRNA expression in two populations of the peacock blenny Salaria pavo with divergent mating systems. Hormones and Behavior. 2010;57(2):155 - 161. doi:10.1016/j.yhbeh.2009.10.007 ...
The teleost brain is characterized by exceptionally high levels of aromatase, the enzyme that converts androgens into estrogens, and by its continuous growth throughout life. Gonadal estrogens have been implicated in sex differentiation and the control of reproduction in adult fish, but the role of neural estrogens during early development is far from clear. The present study describes the isolation and characterization of the cDNA sequence from brain aromatase (P450aromB) in the European sea bass (Dicentrarchus labrax L.), a well established model for neuroendocrine research in fish. P450aromB was cloned from a brain cDNA library and encoded a predicted protein of 505 residues, with a calculated molecular weight of 57.2 kDa. Comparisons of the deduced amino acid sequence to that of the ovarian aromatase (P450aromA) in the same species revealed 62% identity, lower than the 84% identity shared between sea bass and tilapia brain aromatases. Phylogenetic analysis showed the occurrence of a gene ...
Lymphocytes were isolated from 43 surgical samples of breast cancer after tumor enzyme digestion and Ficoll/Verographine procedure. In all, 23 specimens from lymphocytic-tissue infiltrates were analyzed (in some cases, material from 2 or 3 patients was combined). The ability of tumor-infiltrating lymphocytes (TIL) to convert androstenedione was demonstrated, as evaluated by hard-water release from the androgenic precursor 3H-1beta-androstenedione. In material obtained from menopausal women this ability was higher than in the women of reproductive age. A positive correlation was revealed between the level of androstenedione conversion in TIL and aromatase activity in tumor tissue, while no correlation was shown between androstenedione conversion in TIL and percentage of tumor cells in lymphocytic suspension. The data obtained suggest that factors secreted by a neoplasm are able to induce aromatase gene expression in TIL ...
Background: Ischemic stroke is a sexually dimorphic disease. Sex differences in stroke have been attributed to neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation have shown detrimental effects. The role of sex hormones in stroke is still a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests similar aromatase activity in response to brain injury, as increased aromatase expression is seen in ischemic penumbra in animals. Administration of aromatase inhibitors exacerbates damage in experimental stroke models. However, studies on sex steroids in humans are sorely lacking. Objective of this study was to investigate the contributions of sex steroids to the etiology of sex differences in stroke.. Methods: 253 patients admitted to Hartford Hospital for focal neurological deficit were consented for 24hour blood draw from symptom onset. Stroke was confirmed by CTscan/MRI brain. ...
Background: Local oestrogen production in the brain regulates critical functions including neuronal development, gonadotropin secretion and sexual behaviour. In the mouse brain, a 36 kb distal promoter (l.f) regulates the Cyp19a1 gene that encodes aromatase, the key enzyme for oestrogen biosynthesis. In vitro, promoter l.f interacts with oestrogen receptor alpha (Esr1) and Progesterone receptor (Pgr) to mediate Cyp19a1 mRNA expression and enzyme activity in mouse hypothalamic neuronal cell lines. The in vivo mechanisms that control mammalian brain aromatase expression during fetal and adult development, however, are not thoroughly understood.. Objective and hypotheses: Our aim was to elucidate the basis of the in vivo connection between Esr1, Pgr and Cyp19a1.. Method: Pregnant mice were sacrificed at gestational days 9, 11, 13, 15, 16, 19, 21 and the brain tissues of the foetuses were harvested along with five newborns at the age of postnatal day 2. Esr1KO (female) were also sacrificed and their ...
Purpose : We hypothesize that an early estrogen deficiency accelerates the aging of the optic nerve and predisposes to glaucomatous damage. To begin to test our hypotheses, we sought to determine whether estrogen deprivation is associated with elevated intraocular pressure (IOP) and retinal ganglion cell (RGC) loss in male and female mice. Methods : We obtained breeding pairs of C57BL/6J - aromatase knockout (ArKO) heterozygous mice (Dr. Nabil J. Alkayed; Oregon Health & Science University, Portland, OR) to generate homozygous ArKO mice and their wildtype (WT) controls. The homozygous ArKO mice harbored a targeted disruption of exon IX in the cyp19 gene and possess no aromatase activity. Aromatase catalyzes the conversion of androstenedione to estrone and the conversion of testosterone to estradiol. At 12 and 24 weeks of age, we measured in a masked fashion the IOP (n = 6 consecutive IOP measurements/value, 3 values/eye/day, 2 consecutive days) in the left and right eyes of conscious mice (n = ...
Before a woman reaches menopause, the female hormone estrogen is produced in the ovaries. Post menopause however, the woman is no longer releasing eggs via the ovaries, and so estrogen levels are lower. The body has to compensate to this change and does so in the form of an enzyme called aromatase. Aromatase can be found in fat cells and can efficiently convert androgens (another hormone) into estrogen. The More fat someone carries, the more aromatase they have, which leads to more androgens being converted into estrogen. This spike in estrogen is a main cause in breast cancer and would explain why post menopausal woman who are obese are more susceptible to breast cancer ...
250 µCi quantities of Androst-4-ene-3, [1,2,6,7-3H(N)]-, 17-Dione are available for your research. Application of [3H] Androstenedione can be found in: effects of HCG and PMS on bioconversion in steroid biochemistry, breast cancer cell research, inhibition study of human placental aromatase in steroid biochemistry, in vitro metabolism studies in steroid chemistry; etc. ...
TY - JOUR. T1 - Immunocytochemical Localization of Cytochromes P450 17α-Hydroxylase and Aromatase in Embryonic Cell Layers of Elongating Porcine Blastocysts. AU - Conley, Alan J. AU - Christenson, L. K.. AU - Ford, S. P.. AU - Christenson, R. K.. PY - 1994/12. Y1 - 1994/12. N2 - Localized expression of cytochromes P450 17α-hydroxylase (P450c17) and aromatase (P450arom) was investigated in embryonic cell layers of elongating porcine blastocysts by immunocytochemistry. Blastocysts were flushed from the uterus on day 12 of pregnancy, fixed in para-formaldehyde, embedded in paraffin, sectioned, and stained using immunogold- and peroxidase-based techniques. Staining for both P450c17 and P450arom was intense in spherical 7- to 10-mm blastocysts, but was absent in earlier stage 2- to 4-mm blastocysts and less intense or absent in later stage 20-mm and filamentous embryos. Cytochrome P450c17 was limited to the trophoblast of all blastocysts expressing the enzyme, and in spherical 7- to 10-mm ...
The aromatase enzyme (CYP19A1) is required for the biosynthesis of estradiol, a steroid needed for normal follicular and luteal cell function and essential for...
One of the major drawback of aromatase inhibitors, a class of drugs, commonly used in the management of estrogen receptor-positive (ER+) breast cancer is the debilitating joint pain.
The interaction between breast tumor epithelial and stromal cells is vital for initial and recurrent tumor growth. While breast cancer-associated stromal cells provide a favorable environment for proliferation and metastasis, the molecular mechanisms contributing to this process are not fully understood. Nuclear receptors (NRs) are intracellular transcription factors that directly regulate gene expression. Little is known about the status of NRs in cancer-associated stroma. Nuclear Receptor Low-Density Taqman Arrays were used to compare the gene expression profiles of all 48 NR family members in a collection of primary cultured cancer-associated fibroblasts (CAFs) obtained from estrogen receptor (ER)α positive breast cancers (n = 9) and normal breast adipose fibroblasts (NAFs) (n = 7). Thirty-three of 48 NRs were expressed in both the groups, while 11 NRs were not detected in either. Three NRs (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1); ...
Estrogen plays a pivotal role in endometrial cancer etiology. After menopause, estrogen is produced primarily in adipose tissue, and production increases with advancing age as well as with increased body weight (14). It has been suggested that the increase in estrogen production associated with aging results from an increase in the specific activity of the aromatase enzyme in adipose cells, whereas the increase as a function of body weight is simply due to increased numbers of adipose cells (14, 15). In this large pooled analysis, we found that carrying the A allele of rs749292 or rs727479 in CYP19A1 was associated with increased risk of endometrial cancer. Furthermore, we found that the risk was more pronounced in older women (age ≥55 years) and among obese women (BMI ≥30 kg/m2), consistent with the biology of age and obesity on estrogen production.. Our findings were generally consistent with those of the earlier study that found that associations with circulating estrogen levels were ...
Materials and methods Cultures of human THP-1 were activated to macrophages by interferon γ (IFNγ) (500 U/ml) and treated for 24 h with calcitriol (10−8M) and 17β-estradiol (E2, 10−8M) alone and in combination.Untreated macrophages (THP-1-activated) were used as controls (cnt). P450-aromatase synthesis was evaluated by immunocytochemistry (ICC) and western blotting (WB), whereas the expression of the related CYP19A1 gene was quantified by Real-Time PCR (RT-PCR). IL-1β, IL-6 and TNFα synthesis was analysed by enzyme immunoassay (ELISA) and WB. The signal transduction pathway of mitogen activated proteins ERK1/2 was evaluated by WB.. ...
Vitamin D3 - This is key to building up testosterone levels. Most commonly we get D3 via the sun, but either due to location, or modern living, not a lot of us get the recommended amount. It is great for testosterone as it regulates the aromatase enzyme which is responsible for estrogen production.. Vitamin B6 - Affecting the production of testosterone both directly and indirectly - Vitamin B6 boosts testosterone and regulates androgens (the steroid-hormone precursor to testosterone).. Vitamin B9 - Raises energy levels and cognitive function, it does does this by lowering homocysteine levels which have been linked to cognitive impairment.. Vitamin B12 - Essential to producing DNA, hormones and red blood cells. Fats and carbohydrates are processed by making great use of B12.. Sodium - This is probably to work with the nitratine later on in the product to make sodium nitrate. On its own sodium can actually weaken erections by drawing fluid away from areas the body to be absorbed by the salt. This ...
TY - JOUR. T1 - Hsp90 and PKM2 drive the expression of aromatase in Li-Fraumeni syndrome breast adipose stromal cells. AU - Subbaramaiah, Kotha. AU - Brown, Kristy A.. AU - Zahid, Heba. AU - Balmus, Gabriel. AU - Weiss, Robert S.. AU - Herbert, Brittney-Shea. AU - Dannenberg, Andrew J.. PY - 2016/7/29. Y1 - 2016/7/29. N2 - Li-Fraumeni syndrome (LFS) patients harbor germ line mutations in the TP53 gene and are at increased risk of hormone receptor-positive breast cancers. Recently, elevated levels of aromatase, the rate-limiting enzyme for estrogen biosynthesis, were found in the breast tissue of LFS patients. Although p53 down-regulates aromatase expression, the underlying mechanisms are incompletely understood. In the present study, we found that LFS stromal cells expressed higher levels of Hsp90 ATPase activity and aromatase compared with wild-type stromal cells. Inhibition of Hsp90 ATPase suppressed aromatase expression. Silencing Aha1 (activator of Hsp90 ATPase 1), a cochaperone of Hsp90 ...
TY - JOUR. T1 - Adipose stromal cells differentiation toward smooth muscle cell phenotype diminishes their vasculogenic activity due to induction of activin A secretion. AU - Merfeld-Clauss, Stephanie. AU - Lease, Benjamin R.. AU - Lu, Hongyan. AU - March, Keith L.. AU - Traktuev, Dmitry O.. PY - 2017/11. Y1 - 2017/11. N2 - Adipose stromal cells (ASCs) support endothelial cell (EC) vasculogenesis through paracrine and cell-contact communications. In addition, ASCs differentiate towards the smooth muscle cell (SMC) phenotype under different stimuli, which prompted their use as a source of mural cells in fabricating small calibre vessels. How ASCs SMC-lineage commitment affects their subsequent communication with ECs is unknown. The vasculogenic characteristics of human ASCs in progenitor stage and after differentiation towards SMC phenotype were analysed in the present study. Exposure to transforming growth factor β1 (TGFβ1) or activin A has induced expression of SMC markers in ASCs. Analysis ...
Aromatase inhibitors (AI) are medications that inhibit the aromatase enzyme, which converts androgens to estrogens, resulting in suppression of estrogen production in postmenopausal women. Treatment of postmenopausal women diagnosed with hormone receptor positive breast cancer with adjuvant AI therapy for 5 years has resulted in significant improvements in disease free and overall survival. Despite their proven benefit, however, adherence to and persistence with AI therapy is poor. A key reason for non-persistence with therapy is the development of bothersome side effects that can have a negative impact on quality of life. Retrospective analyses have identified possible predictors of poor tolerance of therapy. Studies have also suggested that development of toxicity may be associated with better response to therapy. Because of the concern about non-persistence with therapy, especially in the setting of prescription of an oral medication for many years, there has been considerable research into ...
Methods Female patients referred for BMD estimation in a scanner in the North West of England between 2004 and 2014 on aromatase inhibitors were identified from a dual X-ray absorptiometry database. Demographics and other risk factors, as well as fragility fractures, were recorded. Initially, those who had sustained a fracture were compared to those who had not sustained a fracture using chi-squared tests for categorical variables and T-tests for continuous variables. Following that, univariate and multivariate logistic regression models were fitted looking at the predictors of fracture. Variables included age at scan, height, weight, alcohol, smoking, family history, rheumatoid arthritis, secondary osteoporosis as defined by FRAX™, body mass index and steroid exposure, in addition to BMD in the lumbar spine and femoral neck. ...
Aromatase is the enzyme that catalyzes the biosynthesis of estrogens. It is implicated in neuroprotection. The present study investigated aromatase expression in the cerebellum of dogs infected with canine distemper virus (CDV), a disease characterized by demyelination in the white matter of the cerebellum. The presence of CDV infection was confirmed on the basis of histopathology and immunohistochemical localization of CDV antigen in glial cells of the white matter. The number of aromatase immunoreactive astrocytes were significantly (p < 0.05) higher in CDV-infected dogs compared to control dogs. The results suggest that astrocytes respond to invasion and persistence of CDV by means of increased estrogen production. The results also suggest that the high level of estrogen expression is maintained similarly throughout all stages of the disease since the number of aromatase immunoreactive astrocytes did not vary during the different stages of CDV infection. ...
Prostaglandins can be synthesized in an adrenocortical carcinoma, and they can work in an autocrine or paracrine fashion. In rabbit chondrocyte and human squamous carcinoma cell lines, EGF induced the secretion of PGE2 via up-regulation of the activities of phospholipase A2 (PLA2) and COX-2 (Sato et al. 1997, Huh et al. 2003). This may suggest that PGE2 acts as a secondary factor to EGF in the up-regulation of aromatase expression. Therefore, we checked whether PGE2 was secreted from NCI-H295R cells in response to EGF. In this study, NCI-H295R cells secreted PGE2 in response to EGF (Fig. 13), and PGE2 increased aromatase activity to a greater extent than other prostaglandins (Fig. 6). The inhibition of EGF-induced aromatase expression with PGE2 receptor antagonists confirmed that PGE2 is the secondary factor of aromatase expression with EGF (Fig. 14). PGE1 also increased aromatase activity to a degree similar to that of PGE2, but EGF could not stimu- late NCI-H295R cells to secrete a sufficient ...
HRT is systemic therapy, which means that it sends hormones into the bloodstream so they can travel throughout the entire body. The therapy can take the form of a pill; an injection; or a patch, gel, cream, or spray that delivers the hormones through the skin. HRT is different from local estrogen therapy, which is applied to or delivered inside the vagina for direct relief of symptoms such as dryness, irritation, and pain. Local estrogen therapy can take the form of a cream, ring, or suppository-and although some estrogen does make it into the bloodstream, the amount tends to be small. Unlike HRT, it is designed to treat the vaginal area, not to raise hormone levels throughout the body. To learn more about local estrogen therapy, visit our section on Menopausal Symptoms: Vaginal Changes. Youll see other terms frequently associated with HRT. You may hear people talk about bioidentical hormones, which basically means that the hormones have the same chemical structure as those produced by the ...
Multiple epidemiologic and animal studies have established the link between obesity and increased risk for postmenopausal breast cancer. Because obesity is referred to as the epidemic of the 21st century with around 36% of the adult United States women defined as obese and another one third as overweight (1), this disease has a dramatic effect on quality of life as well as on life expectancy in the United States. The estimated increased risk for breast cancer is around 1.3- to 2-fold for obese postmenopausal women as compared with normal-weight postmenopausal women (2, 3). Several mechanisms have been proposed as being responsible for this increased risk for breast cancer. Among those, a well-studied mechanism is altered estrogen biosynthesis, mainly involving increased aromatase expression (4). Aromatase catalyzes the last steps of estrogen biosynthesis from androgens. Estrogen executes its effect mostly by binding to estrogen receptors (ER). Nuclear ERs function as transcription factors and ...
Aromatase enzyme in your body attaches itself to anabolic androgenic steroids and other similar compounds and turns it into some nasty girly hormones. These estrogen-like hormones can result in side effects, including but not limited to water retention, impotency, or growth of breast tissue in men (gynecomastia).. Male athletes and bodybuilders using performance-improvement drugs need to stay careful and precautious about aromatase enzyme in the body and learn about the importance of the right kind of anabolic steroid cycle support. A single unit of the enzyme can turn steroids and other compounds into estrogen that would then hang out in oblique, the male breast tissues, and other parts of the body. The aromatase enzyme waits for Testosterone and other body hormones to pass body and attaches itself to these males hormones as they flow past the tissue in high enzymatic concentrations; aromatase enzyme then move chemical structure of the male hormones and turn them into estrogen-like hormones. In ...
Aromatase enzyme in your body attaches itself to anabolic androgenic steroids and other similar compounds and turns it into some nasty girly hormones. These estrogen-like hormones can result in side effects, including but not limited to water retention, impotency, or growth of breast tissue in men (gynecomastia).. Male athletes and bodybuilders using performance-improvement drugs need to stay careful and precautious about aromatase enzyme in the body and learn about the importance of the right kind of anabolic steroid cycle support. A single unit of the enzyme can turn steroids and other compounds into estrogen that would then hang out in oblique, the male breast tissues, and other parts of the body. The aromatase enzyme waits for Testosterone and other body hormones to pass body and attaches itself to these males hormones as they flow past the tissue in high enzymatic concentrations; aromatase enzyme then move chemical structure of the male hormones and turn them into estrogen-like hormones. In ...
The synthesis of a series of N-alkylated 4-(4()aminobenzyl)-2-oxazolidinones is described using a synthetically useful scheme which avoids the use of phosgene-since the derivatization is undertaken with the oxazolidin-2-one ring intact. The compounds were tested for human placental aromatase (AR) inhibition in vitro, using [1beta,2beta-3H]androstenedione as substrate for the AR enzyme. The compounds were found, in general, to be more potent than the standard compound, aminoglutethimide (AG), and as such proved to be good lead compounds in the search for more specific AR inhibitors.. ...
Testosterone - the primary substrate in the male body, which serves for the synthesis of estrogen (estradiol), the main female sex hormone. Despite the fact that the presence of estrogen may seem quite uncommon in men, this hormone is structurally very similar to testosterone. With a slight change in the enzyme aromatase, estrogen and can be produced in male organism. Aromatase activity in various parts of the body man, including adipose tissue, liver, sex organs, the organs of the central nervous system and in skeletal muscle tissues. The average number of healthy male estrogen produced usually not particularly affect the body, and may even be beneficial due to its effect on cholesterol levels. However, large amounts of it really has the potential for side effects, including such as water retention, the development of breast (gynaecomastia) and fat accumulation. For these reasons, many people prefer to minimize the intake of estrogenic activity of aromatase inhibitors such as Arimidex and ...
The medial amygdala (MeA) is a central node in the interwoven circuits that regulate social behavior based on pheromones. Aromatase-expressing (arom+) neurons in the MeA are key for the establishment and maintenance of sex differences. Here, we characterized the intrinsic electrophysiological properties of arom+ neurons and non-aromatase (arom-) neurons in the MeA of male and female mice. Most electrophysiological properties were similar for arom+ neurons in the MeA between sexes, but the relative refractory period was twice as large in female mice. We also show that the firing pattern and firing frequency is markedly different between arom+ and arom- neurons. The activity of MeA neurons could be modulated by estradiol, which reduced activity in arom+ neurons in males. The differences between arom+ and arom- neurons were observed in both sexes suggesting that aromatase expression delineates a neural population in the MeA with similar and unique electrophysiological properties.
Aromatase deficiency (AD) is a very rare disorder resulting from mutations in the CYP19A1 gene encoding aromatase, a cytochrome P450 enzyme that plays a pivotal role in androgen conversion to estrogens. AD is inherited in an autosomal recessive trait, and to date only 35 cases have been described in the literature. Herein, we depict a new patient reared as a male, who presented at the age of 21 years with no palpable testis, hypoplastic scrotum, penis-like phallus (3 cm), and penoscrotal hypospadias. The patient was born to consanguineous parents, his karyotype was 46,XX, and SRY was negative ...
The aim of the study is to establish the short-term efficacy and safety of aromatase inhibition in restoring and maintaining eugonadism in hypogonadotrophic hypogonadal men. Secondary aim is to detect the short-term somatic and psychological effects.. Study design: Double blind randomized placebo-controlled trial.. Treatment: 26 weeks of either letrozole or placebo. All patients will start on 1 tablet per week, dose adjustments will be performed if serum testosterone or estradiol are outside the target range. All men will be prescribed a mildly hypocaloric diet.. Endpoints: BMI, body weight, waist circumference, body composition, exercise capacity, serum levels of several hormone markers, glucose tolerance, psychological characteristics.. All patients will be measured 6 times during the study. ...
Fadrozole is a nonsteroidal aromatase inhibitor with potential antineoplastic activity. Fadrozole specifically inhibits aromatase, blocking the aromatization of androstenedione and testosterone into estrone and estradiol, respectively, the final step in estrogen biosynthesis; the reduction in estrogen levels may inhibit growth in estrogen-dependent cancers. Aromatase, a member of the cytochrome P-450 superfamily, is found in many tissues; overexpression has been linked to the development of preneoplastic and neoplastic changes in breast tissue. Check for active clinical trials or closed clinical trials using this agent.
Increased estrogen production and/or action can occur at the testicular level or at the periphery and is characterized as follows: From the testes - Can be due to testicular tumors or to ectopic prod... more
The result of anastrozole on peripheral and tumour aromatase activity and oestrogen levels in postmenopausal patients with oestrogen receptor-rich breast tumours was investigated. (92?:?8), and put through chromatography on Sephadex LH-20. Fractions filled with either E1 or oestradiol (E2) had been after that evaporated to dryness and analysed by radioimmunoassay as defined previously (Thijssen aromatase, and aromatase activity continued to be undetectable in four tumours. (The d.p.m. in the oestrone fractions counted from on-treatment sufferers had been 3H C1 to 5 (aside from an individual tumour using a worth of 13) and 14C 15 to 40.) The difference between pre-treatment and treated specimens was significant (aromatase activity pre-treatment statistically. It is worth taking into consideration the great reason behind the shortcoming to detect a definite decrease in activity using tumours. The known fact that, in each one of the individuals, peripheral aromatase was profoundly affected by ...
E-BRAKE - THE WORLDS STRONGEST NATURAL ANTI-ESTROGEN COMPOUND Estrogen production is the product of the aromatase enzyme that converts testosterone into estrogen. Like the e-brake in a high performance vehicle, Magnum E-Brake is scientifically formulated to slow estrogen production with extreme precision. The bene
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Differently substituted 3,4-dihydropyrimidinones were prepared using a three component Biginelli reaction. By using a model compound 124-I-b, extensive preliminary research was done in order to find a new appropriate 3,4-dihydropyrimidinone aromatization method. A wide range of reaction conditions, reagents, catalysts and solvents were examined. The scope of the preliminary examination supports the literature known fact that this kinds of compounds are very difficult to be aromatized. The research in the context of this PhD thesis has resulted in four new, so far unknown methods of 3,4-dihydropyrimidinone aromatization. Efficient, rapid and selective aromatization method was developed using molecular iodine and potassium t-butoxide in dry tetrahydrofuran at room temperature (conversion 80 % - 100 %). 3,4-Dihydropyrimidinone aromatization mechanism was proposed. It includes the formation of t-butil hypoiodite as an active species during aromatization. The second aromatization method is catalytic ...
Interest in these adipose interactions has provoked contemporaneous investigations using independent approaches to track the relationship of ILC2s with tissue reservoirs of IL-33. Mahlakõiv et al. (2019) used IL-33 reporter mice to identify a similar population of adipose stromal cells, designated adipose stem and progenitor cells, as well as a lesser population of podoplanin+PDGFRα- stromal cells in the fat pad-enveloping mesothelium. High-fat diet induced rapid IL-33 loss from adipose stem and progenitor cells and protection from the increases in weight and adipocyte numbers seen in the absence of IL-33 or ST2. The authors suggested that IL-33 from mesothelial lining cells might function more as an alarmin released after tissue perturbation through expansion or injury. Spallanzani et al. (2019), with a long interest in adipose ST2+ T reg cells, also localized IL-33 predominantly to adipose PDGFRα+Sca1+ stromal and mesothelial cells, but single-cell RNA sequencing (RNA-seq) and bulk RNA-seq ...
Life has been full of weirdness lately. Part of the weirdness is my trying to decide if I wanted to apply for a spot in a trial cancer treatment. I admit, that when my oncologist told me that my tumor markers had doubled at the beginning of the month, I was put into a tailspin. He has put me on Tamoxifen because sometimes, when youve been on aromatase inhibitors (like aromasin and arimidex) which have failed, you can fool the cancer into accepting Tamoxifen again and then it dies off. The process, however, takes two months to see if it works or not and it may cause cancer flare ups initially ...
Since a lot of the aromatase enzyme is present in adipose tissue, do you believe that it would make sense that a person with a higher body fat, lets say 15% wil have mroe estrogen than a person who is 7% bf. If so can you also conclude that a person with higher bodyfat will have a harder pct then a person with lower body fat due to decreased estrogen.??
Hormones are powerful and complex. The word to describe these fascinating chemicals is originally derived from hormo, a Greek word meaning to set in motion. Hormones set the bodys processes in motion, touching + stimulating nearly every biological system. And estrogen, by far, is one of the most impressive. In a w
Arko Essential Purifying Spray is a mix of 50 essential oils that help you breathe easily by purifying and cleansing your environment. The...
The compound has the following spectroscopic characteristics: 1HNMR(400 MHz, CDC13): δppm= 1.14 (s, 3H, Me), 1.25 (bs, 4H, Me + OH), 1.67 (s, 3H, Me), 1.87 (ddd, 1H, J, = 13.9 Hz, J2 = 11.1 Hz, J3 = 2.5 Hz, C6-H), 1.93 (d, 3H, J= 0.8 Hz, Me), 2.08 (d, 2H, J = 8.8 Hz, C14-H2), 2.24 (s, 3H, Me), 2.26 (s, 3H, Me), 2.55 (m, 2H, C6-H + C7-OH), 3.28 (d, 1H, J= 8.4 Hz, C2-OH), 3.77 (d/lH, /= 7.2 Hz, C3-H), 4.15 (dd, 1H, J, = 8.2 Hz, J2= 0.8 Hz, C20-H), 4.28 (d, 1H, J= 8.2 Hz, C20-H), 4.41 (m, 2H, C7-H + C21-H), 4.93 (dd, 1H, J, = 9.6 Hz, J2 = 2.0 Hz, C5-H), 4.96 (d, 1H, J = 4.4 Hz, C3-H), 5.64 (d, 1H, J= 7.2 Hz, C2-H), 6.17 (dt, 1H, J, - 7.9 Hz, J2 = 1.2 Hz, C13-H), 6.30 (s, 1H, C10-H), 7.46-7.32 (m, 5H, arom), 7.46-7.32 (m, 5H, arom), 7.50 (m, 2H, arom), 7.63 (m, 1H, arom), 8.06 (m, 2H, arom); 13C NMR (100 MHz, CDC13): δppm= 9.8, 15.3, 21.1, 21.9, 22.6, 27.0, 35.6, 35.8, 43.3, 45.9, 58.8, 68.1, 72.0, 72.4, 75.1, 75.3, 75.8, 76.7, 79.4, 81.3, S4.6, 127.9, 128.9, 129.2, 129.5, 130.3, 133.4, 134.1, ...
Aromāts dāvanu komplektu Ladies Collection miniatūras 2 • Kosmētikas komplekti • Parfimērija un kosmētika, cenas tiešsaistē lētāk.
Inibidores da aromatase[editar , editar código-fonte]. Os inibidores da aromatase (IA) são recomendados para o uso em cânceres ... A BRCA1 regula a expressão da aromatase através do promotor I3/II e está sendo analisada sua possível função como preditor da ... de mama responsivos ao estrogênio, visto que a aromatase é responsável pela produção de estrógeno. Possui destaque devido ao ...
It can be used at a dosage of up to 500 mg four times per day (2,000 mg/day). It is used as an aromatase inhibitor to inhibit ... Maximal aromatase inhibition is said to occur between dosages of 250 to 500 mg per day. The side effects of AG are less ... AG can inhibit aromatase by 74 to 92% and decrease circulating estradiol levels by 58 to 76% in men and postmenopausal women. ... In any case, AG is also used by bodybuilders and other men for its actions as an aromatase inhibitor in order to decrease ...
Aromatase inhibitors like exemestane (which forms a permanent and deactivating bond with the aromatase enzyme) and anastrozole ... Lephart, E. D. (1996). "A review of brain aromatase cytochrome P450". Brain Res. Rev. 22 (1): 1-26. doi:10.1016/0165-0173(96) ... Avendaño, C.; Menéndez, J. C. (2008). "Aromatase Inhibitors". Medicinal Chemistry of Anticancer Drugs. Elsevier. pp. 65-73. doi ... A related aromatization process includes dehydroisomerization of methylcyclopentane to benzene: Aromatases are enzymes that ...
Aromatase and estrogenicityEdit. Testosterone can be metabolized by aromatase into estradiol, and many other AAS can be ... AROM = Metabolized by aromatase. 3-HSD = Metabolized by 3α- and/or 3β-HSD. Estr = Estrogenic. Prog = Progestogenic. Oral = Oral ... Roselli CE (1998). "The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat ... Aside from 5α-reductase, aromatase may inactivate testosterone signaling in skeletal muscle and adipose tissue, so AAS that ...
steroid biosynthesis: aromatase synthesizes estrogen. 1 subfamily, 1 gene. CYP19A1 CYP20. unknown function. 1 subfamily, 1 gene ... CYP19A (P450arom, aromatase) in endoplasmic reticulum of gonads, brain, adipose tissue, and elsewhere catalyzes aromatization ... Some CYPs metabolize only one (or a very few) substrates, such as CYP19 (aromatase), while others may metabolize multiple ... Aromatase. Clozapine, imipramine, paracetamol, phenacetin Heterocyclic aryl amines Inducible and CYP1A2 5-10% deficient oxidize ...
Aromatase. ,100 μM. -. 0% For reference, circulating concentrations of danazol are in the range of 2 μM at a dosage of 600 mg/ ... another study found that danazol weakly inhibited aromatase as well, with 44% inhibition at a concentration of 10 μM.[32] ...
ASL Aromatase deficiency; 613546; CYP19A1 Aromatase excess syndrome; 139300; CYP19A1 Aromatic L-amino acid decarboxylase ...
... aromatase, on breast cancer. Brodie managed to get an aromatase inhibitor into a limited clinical trial in breast cancer ... aromatase. They developed several steroidal aromatase inhibitors, she focused on 4-OHA. In 1979, she moved to Maryland, ... She never intended to retire, and collaborated with Vincent Njar on aromatase inhibitors in prostate cancer for the rest of her ... She presented a paper on her aromatase inhibitors at a Rome conference in 1980, which led to collaboration with Charles Coombes ...
In competitive inhibition, an inhibitor that resembles the normal substrate binds to the enzyme, usually at the active site, and prevents the substrate from binding.[8] At any given moment, the enzyme may be bound to the inhibitor, the substrate, or neither, but it cannot bind both at the same time. During competitive inhibition, the inhibitor and substrate compete for the active site. The active site is a region on an enzyme which a particular protein or substrate can bind to. The active site will only allow one of the two complexes to bind to the site therefore either allowing for a reaction to occur or yielding it. In competitive inhibition the inhibitor resembles the substrate therefore taking its place and binding to the active site of an enzyme. Increasing the substrate concentration would diminish the "competition" for the substrate to properly bind to the active site and allow a reaction to occur.[3] When the substrate is of higher concentration than that of the competitive inhibitor, it ...
Aromatase inhibitors. *Non-selective: Aminoglutethimide. *Testolactone. *Selective: Anastrozole. *Exemestane. *Fadrozole. * ...
Aromatase inhibitors. *Non-selective: Aminoglutethimide. *Testolactone. *Selective: Anastrozole. *Exemestane. *Fadrozole. * ...
Mainly CYP3A4 (liver);[1] also 5α-/5β-reductase, 3α-/3β-HSD, and aromatase. ... Norethisterone and its major active metabolite 5α-DHNET have been found to act as irreversible aromatase inhibitors (Ki = 1.7 ... Yamamoto T, Tamura T, Kitawaki J, Osawa Y, Okada H (1994). "Suicide inactivation of aromatase in human placenta and uterine ... A small amount of norethisterone is also converted by aromatase into EE.[2][4][36] Norethisterone is metabolized in the liver ...
The COX-2 enzyme was discovered in 1988 by Daniel Simmons, a Brigham Young University researcher.[23] The mouse COX-2 gene was cloned by UCLA scientist Dr. Harvey Herschman, a finding published in 1991.[24]. The basic research leading to the discovery of COX-2 inhibitors has been the subject of at least two lawsuits. Brigham Young University has sued Pfizer, alleging breach of contract from relations BYU had with the company at the time of Dr. Simmons's work.[25][26] A settlement was reached in April 2012 in which Pfizer agreed to pay $450 million.[27][28] The other litigation is based on United States Pat. No. 6,048,850[29] owned by University of Rochester, which claimed a method to treat pain without causing gastro-intestinal distress by selectively inhibiting COX-2. When the patent issued, the university sued Searle (later Pfizer) in a case called, University of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004). The court ruled in favor of Searle in 2004, holding in essence that ...
A 2017 population-based, matched-cohort study of 93,197 men aged 66 years and older with BPH found that finasteride and dutasteride were associated with a significantly increased risk of depression (HR, 1.94; 95% CI, 1.73-2.16) and self-harm (HR, 1.88; 95% CI, 1.34-2.64) during the first 18 months of treatment, but were not associated with an increased risk of suicide (HR, 0.88; 95% CI, 0.53-1.45).[31][32][33][21] After the initial 18 months of therapy, the risk of self-harm was no longer heightened, whereas the elevation in risk of depression lessened but remained marginally increased (HR, 1.22; 95% CI, 1.08-1.37).[31][32][21] The absolute increase in the rate of depression was 247 per 100,000 patient-years and of self-harm was 17 per 100,000 patient-years.[21][34] As such, on the basis of these findings, it has been stated that cases of depression in patients that are attributable to 5-ARIs will be encountered on occasion, while cases of self-harm attributable to 5-ARIs will be encountered ...
Although aromatase inhibitors and antigonadotropins can be considered antiestrogens by some definitions, they are often treated ... Riggins RB, Bouton AH, Liu MC, Clarke R (2005). "Antiestrogens, aromatase inhibitors, and apoptosis in breast cancer". Vitam. ... aromatase inhibitors (AIs) like anastrozole, and antigonadotropins including androgens/anabolic steroids, progestogens, and ... "Signaling Pathways of Apoptosis Activated by Aromatase Inhibitors and Antiestrogens". The Journal of Cancer Research ...
The affinity of RI for ribonucleases is among the highest for any protein-protein interaction; the dissociation constant of the RI-RNase A complex is in the femtomolar (fM) range under physiological conditions while that for the RI-angiogenin complex is less than 1 fM. Despite this high affinity, RI is able to bind a wide variety of RNases A despite their relatively low sequence identity. Both biochemical studies and crystallographic structures of RI-RNase A complexes suggest that the interaction is governed largely by electrostatic interactions, but also involves substantial buried surface area.[3][4] RI's affinity for ribonucleases is important, since many ribonucleases have cytotoxic and cytostatic effects that correlate well with ability to bind RI.[5] Mammalian RIs are unable to bind certain pancreatic ribonuclease family members from other species. In particular, amphibian RNases, such ranpirnase and amphinase from the Northern leopard frog, escape mammalian RI and have been noted to have ...
Beyond being a catalyst in the rate-limiting step in testosterone reduction, 5α-reductase isoforms I and II reduce progesterone to 5α-dihydroprogesterone (5α-DHP) and deoxycorticosterone to dihydrodeoxycorticosterone (DHDOC). In vitro and animal models suggest subsequent 3α-reduction of DHT, 5α-DHP and DHDOC lead to neurosteroid metabolites with effect on cerebral function. These neurosteroids, which include allopregnanolone, tetrahydrodeoxycorticosterone (THDOC), and 3α-androstanediol, act as potent positive allosteric modulators of GABAA receptors, and have antidepressant, anxiolytic, prosexual, and anticonvulsant effects.[33] 5α-Dihydrocortisol is present in the aqueous humor of the eye, is synthesized in the lens, and might help make the aqueous humor itself.[34] 5α-Dihydroaldosterone is a potent antinatriuretic agent, although different from aldosterone. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium.[35] 5α-DHP is a ...
Aromatase inhibitors. *Non-selective: Aminoglutethimide. *Testolactone. *Selective: Anastrozole. *Exemestane. *Fadrozole. * ...
Aromatase inhibitors. *First-generation: Aminoglutethimide. *Testolactone. *Second-generation: Fadrozole. *Formestane. *Third- ...
The role of cholesterol in the development of cardiovascular disease was elucidated in the second half of the 20th century.[138] This lipid hypothesis prompted attempts to reduce cardiovascular disease burden by lowering cholesterol. Treatment consisted mainly of dietary measures, such as a low-fat diet, and poorly tolerated medicines, such as clofibrate, cholestyramine, and nicotinic acid. Cholesterol researcher Daniel Steinberg writes that while the Coronary Primary Prevention Trial of 1984 demonstrated cholesterol lowering could significantly reduce the risk of heart attacks and angina, physicians, including cardiologists, remained largely unconvinced.[139] Scientists in academic settings and the pharmaceutical industry began trying to develop a drug to reduce cholesterol more effectively. There were several potential targets, with 30 steps in the synthesis of cholesterol from acetyl-coenzyme A.[140] In 1971, Akira Endo, a Japanese biochemist working for the pharmaceutical company Sankyo, ...
When used in the central nervous system to alleviate neurological symptoms, such as rivastigmine in Alzheimer's disease, all cholinesterase inhibitors require doses to be increased gradually over several weeks, and this is usually referred to as the titration phase. Many other types drug treatments may require a titration or stepping up phase. This strategy is used to build tolerance to adverse events or to reach a desired clinical effect.[12] This also prevents accidental overdose and is therefore recommended when initiating treatment with drugs that are extremely potent and/or toxic (drugs with a low therapeutic index). ...
Aromatase deficiency is ultimately suspected which is involved in the synthesis of estrogen in humans and has therapeutic ... Rochira V, Carani C (October 2009). "Aromatase deficiency in men: a clinical perspective". Nature Reviews. Endocrinology. 5 (10 ... When estrogen levels were raised through the increased activity of the enzyme aromatase in male lab mice, OCD rituals were ... Ryan KJ (August 1982). "Biochemistry of aromatase: significance to female reproductive physiology". Cancer Research. 42 (8 ...
In response to a report of precancerous changes in the pancreases of rats and organ donors treated with the DPP-4 inhibitor sitagliptin,[21][22] the United States FDA and the European Medicines Agency each undertook independent reviews of all clinical and preclinical data related to the possible association of DPP-4 inhibitors with pancreatic cancer. In a joint letter to the New England Journal of Medicine, the agencies stated that they had not yet reached a final conclusion regarding a possible causative relationship.[23]. A 2014 meta-analysis found no evidence for increased pancreatic cancer risk in people treated with DPP-4 inhibitors, but owing to the modest amount of data available, was not able to completely exclude possible risk.[24]. ...
As enzymes have evolved to bind their substrates tightly, and most reversible inhibitors bind in the active site of enzymes, it is unsurprising that some of these inhibitors are strikingly similar in structure to the substrates of their targets. An example of these substrate mimics are the protease inhibitors, a very successful class of antiretroviral drugs used to treat HIV.[19] The structure of ritonavir, a protease inhibitor based on a peptide and containing three peptide bonds, is shown on the right. As this drug resembles the protein that is the substrate of the HIV protease, it competes with this substrate in the enzyme's active site. Enzyme inhibitors are often designed to mimic the transition state or intermediate of an enzyme-catalyzed reaction. This ensures that the inhibitor exploits the transition state stabilising effect of the enzyme, resulting in a better binding affinity (lower Ki) than substrate-based designs. An example of such a transition state inhibitor is the antiviral drug ...
Aromatase inhibitors. *Non-selective: Aminoglutethimide. *Testolactone. *Selective: Anastrozole. *Exemestane. *Fadrozole. * ...
Aromatase inhibitors (e.g., anastrozole). *GnRH agonists (e.g., GnRH). Antigonadotropins. *Sex steroid agonists (via negative ...
A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of trypsin by controlling the activation and catalytic reactions of proteins.[1] Trypsin is an enzyme involved in the breakdown of many different proteins, primarily as part of digestion in humans and other animals such as monogastrics and young ruminants. When trypsin inhibitor is consumed it acts as an irreversible and competitive substrate.[2] It competes with proteins to bind to trypsin and therefore renders it unavailable to bind with proteins for the digestion process.[1] As a result, protease inhibitors that interfere with digestion activity have an antinutritional effect. Therefore, trypsin inhibitor is considered an anti-nutritional factor or ANF.[3] Additionally, trypsin inhibitor partially interferes with chymotrypsin function. Trypsinogen is an inactive form of trypsin, its inactive form ensures protein aspects of the body, such as the pancreas and muscles, are ...
Aromatase inhibitors. *First-generation: Aminoglutethimide. *Testolactone. *Second-generation: Fadrozole. *Formestane. *Third- ...
Researchers are investigating whether protease inhibitors could possibly be used to treat cancer. For example, nelfinavir and atazanavir are able to kill tumor cells in culture (in a Petri dish).[11][12] This effect has not yet been examined in humans; but studies in laboratory mice have shown that nelfinavir is able to suppress the growth of tumors in these animals, which represents a promising lead towards testing this drug in humans as well.[12] Inhibitors of the proteasome, such as bortezomib are now front-line drugs for the treatment of multiple myeloma. Tanomastat is one of the matrix metalloproteinase inhibitors that can be used to treat cancer. ...
Numerous TKIs aiming at various tyrosine kinases have been generated by the originators of these compounds and proven to be effective anti-tumor agents and anti-leukemic agents.[4][5] Based on this work imatinib was developed against chronic myelogenous leukemia (CML)[6] and later gefitinib and erlotinib aiming at the EGF receptor. Sunitinib, an inhibitor of the receptors for FGF, PDGF and VEGF is also based on early studies on TKIs aiming at VEGF receptors.[7] Adavosertib is a Wee1 kinase inhibitor that is undergoing numerous clinical trials in the treatment of refractory solid tumors.[8] However, toxicities such as myelosuppression, diarrhea, and supraventricular tachyarrhythmia have arisen while attempting to determine the toxicity and effectiveness of the drug.[9] Lapatinib, FDA approved for treatment in conjunction with chemotherapy or hormone therapy, is also currently undergoing clinical trials in the treatment of HER2-overexpressing breast cancers as it is suggested intermittent ...
Aromatase deficiency is a condition characterized by reduced levels of the female sex hormone estrogen and increased levels of ... the male sex hormone testosterone.Females with aromatase deficiency have a typical female chromosome pattern (46,XX) but are ... CYP19A1 gene mutations that cause aromatase deficiency decrease or eliminate aromatase activity. A shortage of functional ... Females with aromatase deficiency have a typical female chromosome pattern (46,XX. ) but are born with external genitalia that ...
In particular, aromatase is responsible for the aromatization of androgens into estrogens. The enzyme aromatase can be found in ... Aromatase activity is decreased by prolactin, anti-Müllerian hormone, and the common herbicide glyphosate. Aromatase activity ... "Aromatase Inhibitors". Attar E, Bulun SE (May 2006). "Aromatase inhibitors: the next generation of ... Despite the fact that data suggest temperature controls aromatase quantities, other studies have shown that aromatase can ...
Aromatase inhibitors are a class of hormonal agents that form part of the therapy for some types of breast cancer. These agents ... Advantages of using aromatase inhibitors. The advantages of using aromatase inhibitors over other hormonal agents such as ... Aromatase inhibitors are a class of hormonal agents that form part of the therapy for some types of breast cancer. These agents ... Aromatase inhibitors prevent the formation of estrogen and thus reduce the estrogen dependent growth of estrogen receptor (ER) ...
Aromatase deficiency is a very rare condition characterised by the extremely low or absence of the enzyme aromatase activity in ... Aromatase deficient female cannot synthesize estrone or estradiol in the absence of aromatase. The amount of androgen will ... RORA is the gene for aromatase, an enzyme that converts male to female hormones. Thus, RORA deficiency is linked to aromatase ... Aromatase deficient males experience a normal growth into adulthood. With a very low level of circulating estrogen (. ...
... aromatase inhibitors - are more effective than tamoxifen for reducing mortality among women with ER-positive breast cancer. ... Aromatase inhibitors lower estrogen levels by preventing the enzyme aromatase - found in fat tissue - from changing other ... Aromatase inhibitors reduced breast cancer mortality by 40%. For their study, the team analyzed the data of nine clinical ... Aromatase inhibitors remove only the tiny amount of estrogen that remains in the circulation of women after the menopause - but ...
Aromatase is encoded by the CYP19A1 gene and there is no evidence for more than one isoform of aromatase existing in the human ... 3.4.4. Alteration in Aromatase mRNA Levels. In addition to examining aromatase enzyme activity, some reports have shown that ... In general, phytoestrogens act as aromatase inhibitors by (a) decreasing aromatase gene expression, (b) inhibiting the ... reported that the isoflavone, genistein, induced aromatase activity and increased aromatase mRNA expression in hepatic cells ( ...
Discontinuation and nonadherence were higher among breast cancer patients taking brand name aromatase inhibitors (BAIs) vs ... Aromatase inhibitor use has been shown to reduce the risk of breast cancer recurrence. However, studies reported only 40%-60% ... Discontinuation and nonadherence were higher among breast cancer patients taking brand name aromatase inhibitors (BAIs) vs ... Discontinuation and nonadherence were higher among breast cancer patients taking brand name aromatase inhibitors (BAIs) vs ...
This F1000 commentary rates a meta-analysis on aromatase inhibitors and when their use should be discouraged as Changes ... When Are Aromatase Inhibitors Wrong for Breast Cancer Patients? Classified by F1000 as Changes Clinical Practice. ... Changes clinical practice: The risks and benefits of adjuvant aromatase inhibitors (AIs) should be weighed carefully, ... This meta-analysis confirms that an aromatase inhibitor (AI) is not the best therapy for all postmenopausal women with hormone- ...
Pharmaceutical aromatase inhibitorsEdit. Main article: Aromatase inhibitor. Aromatase inhibitors, which stop the production of ... Aromatase deficiency syndromeEdit. Main article: Aromatase deficiency. This syndrome is due to a mutation of gene CYP19 and ... Aromatase excess syndromeEdit. Main article: Aromatase excess syndrome. A number of investigators have reported on a rather ... In particular, aromatase is responsible for the aromatization of androgens into estrogens. The aromatase enzyme can be found in ...
Aromatase inhibitors and tamoxifen are two types of hormonal therapy.. A study found that women diagnosed with early-stage, ... The aromatase inhibitors can weaken bones and make women more likely to break a bone, though this is uncommon. Tamoxifen ... In other cases, women take tamoxifen for 2 or 3 years and then switch to an aromatase inhibitor until the hormonal therapy has ... This study found that broken bones due to hormonal therapy were 47% more likely in women who got 5 years of an aromatase ...
The activity of aromatase regulates the concentrations of estrogens with endocrine, paracrine, and autocrine effects on target ... Moreover, with aging, individual differences in aromatase activity may significantly affect bone loss and fracture risk in men. ... Clinical and experimental evidences clearly indicate that aromatase activity and estrogen production are necessary for ... Aromatase is a specific component of the cytochrome P450 enzyme system responsible for the transformation of androgen ...
More: What Are Aromatase Inhibitors?. In 2005, Breast Cancer Action launched an online survey to collect information from women ... Aromatase inhibitors (AIs) have quickly become standard treatments for postmenopausal women with estrogen-receptor-positive ... These reports are dedicated to the women who generously took the time to respond to BCAs Aromatase Inhibitor Side Effects ... In June 2008, BCA released the follow-up report, Side Effects Revisited: Womens Experiences with Aromatase Inhibitors based on ...
Tag: aromatase inhibitor. AcupunctureCancerClinical Trials. Acupuncture versus breast cancer treatment-induced joint pain: ... The investigators behind a recent clinical trial testing acupuncture to treat joint pain caused by aromatase inhibitors used to ...
Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast ... The first section covers general knowledge about aromatase inhibitors, including regulation of aromatase genes, and structure ... Resistance to Aromatase Inhibitors in Breast Cancer. Editors. * Alexey Larionov Series Title. Resistance to Targeted Anti- ... Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast ...
Tags: 50 to 64, 65 and older, Estrogen-Receptor Positive, Aromatase Inhibitors, Arimidex (chemical name: anastrozole), Aromasin ... Aromatase inhibitors arent commonly used to reduce recurrence risk in premenopausal women. Still, in some cases a ... "The treatment with aromatase inhibitors worked significantly better in the non-smoking patients," she continued. "However, we ... "Smokers who were treated with aromatase inhibitors had a three times higher risk of recurrence of breast cancer compared with ...
Another aromatase inhibitor, androst-4-ene-3,6,17-trione, has been efficiently prepared using PCC on montmorillonite K10, under ... Improved syntheses of aromatase inhibitors and neuroactive steroids efficient oxidations and reductions at key positions for ... Using testosterone as starting material, a new short synthesis of an aromatase inhibitor, 4-OHA, has been achieved through ...
Taking the aromatase inhibitor exemestane (Aromasin) for primary prevention of breast cancer may weaken the bones, researchers ... Aromatase Inhibitor Linked to Bone Loss. Taking the aromatase inhibitor exemestane (Aromasin) for primary prevention of breast ... Taking the aromatase inhibitor exemestane (Aromasin) for primary prevention of breast cancer may weaken the bones, researchers ... Loss of bone density and fractures are known risks of aromatase inhibitors in breast cancer survivors taking the drugs to ...
SEARCH RESULTS for: Aromatase Inhibitors [Drug Class] (65 results) * Share : JavaScript needed for Sharing tools. Bookmark & ...
Aromatase inhibitors after Tamoxifen Ten Year Survival With Aromatase Inhibitor Use Evista as adjuvant therapy DCIS Hormone ... Can aromatase inhibitors be used to prevent reccurrence of malignant mammary tumors in dogs? If so, which one is indicated, and ... Aromatase Inhibitors or Tamoxifen Canine Mammary Tumors & Spaying Drug/Herbal Interactions with Arimidex Tamoxifen Therapy for ... We are not aware of any studies published on the effect of aromatase inhibitors in dogs with mammary carcinoma, but based on ...
nlm:permissions xmlns:nlm= xmlns:hwp=,,nlm:copyright-statement hwp:id=copyright-statement-1,©2009 American Association for Cancer Research.,/nlm:copyright-statement,,nlm:copyright-year,2009,/nlm:copyright-year,,/nlm:permissions ...
... Front Neuroendocrinol. 2009 Jul;30(2):106-18. doi: 10.1016/j.yfrne.2009.04.016. Epub ... We are only beginning to understand the factors responsible for the injury-induced transcription of aromatase in astroglia. In ... However, gaps in our knowledge include issues about the cell-specific regulation of aromatase expression, steroidal influences ... The induced expression of aromatase apparently elevates local estrogen levels enough to interfere with apoptotic pathways, ...
Vitamin D3 prevents side effects in breast cancer patients -multiple studies confirm a reduction in side effects of aromatase ... c) a history of generalized musculoskeletal pain that began or worsened since starting treatment with the aromatase inhibitor. ... 3.Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study.Breast Cancer Res Treat. ... Fifty percent of women taking aromatase inhibitors reported musculoskeletal pain, and up to 30% reported fatigue. The results ...
An aromatase-producing sex-cord tumor resulting in prepubertal gynecomastia.. Coen P1, Kulin H, Ballantine T, Zaino R, ...
Biological and clinical effects of aromatase inhibitors in neoadjuvant therapy.. Miller WR1, Dixon JM, Cameron DA, Anderson TJ. ... The results suggest that potent specific aromatase inhibitors will be valuable in treating hormone-dependent cancers. ...
... adjuvant treatment with aromatase inhibitors does not raise the risk for cardiovascular events, a researcher said. ... The aromatase inhibitors are rapidly replacing tamoxifen as the adjuvant treatment of choice for early breast cancer in ... Dickler said, "When youre comparing an [aromatase inhibitor] to tamoxifen, its easy to forget that tamoxifen does have lipid- ... Monnier concluded that comparisons of aromatase inhibitors with placebo may be more useful in determining the risks associated ...
AromataseImported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a href="/ ... Aromatase, EC (CYPXIX) (Cytochrome P-450AROM) (Cytochrome P450 19A1) (Estrogen synthase) ... tr,H0YNJ7,H0YNJ7_HUMAN Aromatase (Fragment) OS=Homo sapiens OX=9606 GN=CYP19A1 PE=1 SV=1 ...
AromataseAdd BLAST. 503. Proteomic databases. PaxDb, a database of protein abundance averages across all three domains of life ... Aromatase1 Publication. ,p>Manually curated information that is based on statements in scientific articles for which there is ... "Isolation and characterization of a complementary deoxyribonucleic acid insert encoding bovine aromatase cytochrome P450.". ... sp,P46194,CP19A_BOVIN Aromatase OS=Bos taurus OX=9913 GN=CYP19A1 PE=2 SV=3 ...
The enzyme that is responsible for this conversion is aromatase, made primarily in fat and other tissue, especially in the ... Also, there will be information from trials testing aromatase inhibitors following 5 years of tamoxifen. The other aromatase ... There are ongoing trials that will anwer the questions of 2-3 years of tamoxifen followed by an aromatase inhibitor. For newly ... The enzyme that is responsible for this conversion is aromatase, made primarily in fat and other tissue, especially in the ...
Buy our Recombinant Human Aromatase protein. Ab112277 is a protein fragment produced in Wheat germ and has been validated in WB ... AEXS is characterized by an estrogen excess due to an increased aromatase activity.. Defects in CYP19A1 are the cause of ... Defects in CYP19A1 are a cause of aromatase excess syndrome (AEXS) [MIM:139300]; also known as familial gynecomastia. ... AROD is a rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, ...
The second part of this is that these things impact the aromatase factor in the body. The aromatase process not only increases ... Tags: aromatase process, increase bio-availability testosterone, increase testosterone naturally, raise testosterone levels ... This type of fat has particularly high levels of the enzyme aromatase, which leads to higher estrogen and SHBG levels. Second, ... Supplements that may help inhibit aromatase in the body include Zinc and Chrysin. ...
  • The aromatase inhibitors include anastrozole (Armidex), letrozole (Femara) and exemastane (Aromasin). (
  • The aromatase inhibitors anastrozole and letrozole are similar in their pharmacokinetic properties and both have a dosing schedule of once daily due to a half life (time taken for a the amount of a drug present in the body to become halved) of approximately 48 hours for each of them. (
  • The other aromatase inhibitors, letrozole (Femara) and exemestane (Aromasin) are also being tested in early stage breast cancer. (
  • Northwestern Memorial Hospital physician publishes findings of pioneering study in February issue of Fertility and Sterility Letrozole (Femara), an aromatase inhibitor currently used to prevent breast cancer recurrence in postmenopausal women, shows promise in the treatment of endometriosis, according to the results of a pioneering pilot study conducted by Serdar Bulun, M.D., chief of the Division of Reproductive Biology Research at Northwestern Memorial Hospital. (
  • The third-generation aromatase inhibitors (AIs)-anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin)-are increasingly being found to improve upon the efficacy we observed for decades with tamoxifen. (
  • Postmenopausal women whose breast cancer is fueled by hormones (estrogen receptor-positive breast cancer) are typically prescribed aromatase inhibitors (AIs), a class of drugs that includes anastrozole, letrozole and exemestane, for five years after surgery or primary treatment. (
  • Among a new line of infertility treatment drugs aimed at balancing hormone levels such as estrogen and testosterone are aromatase inhibitors in the form of anastrozole (Arimidex) and letrozole (Femara). (
  • Aromatase inhibitors used in treating fertility problems are known as letrozole (Femara) and anastrozole (Arimidex). (
  • [email protected] Skype:live:kathelin_4 WhataApp:+8618872220706 Letrozole description: Femara is a powerful Aromatase Inhibitor that was developed to fight breast cancer. (
  • Femara (letrozole) is an extensively investigated, marketed aromatase inhibitor (AI) widely used as treatment in the maintenance phase of estrogen-receptor (ER) positive breast cancer, as it inhibit the synthesis of estrogens. (
  • Tamoxifen works by blocking oestrogen's effects on cells, whereas letrozole, which belongs to a class of drugs called aromatase inhibitors , works by preventing the body from making oestrogen in the first place. (
  • If you have hormone receptor-positive breast cancer, hormone therapy with tamoxifen and/or an aromatase inhibitor (anastrozole, letrozole or exemestane) is a key part of your treatment. (
  • Oestrogen actions are mediated through oestrogen receptor (ER), and endocrine therapies, such as aromatase inhibitors (i.e., letrozole, anastrozole and exemestane) and tamoxifen, are used in patients with ER-positive invasive carcinoma to block the oestrogen actions. (
  • Originally used in the treatment of breast cancer and prostate cancer, aromatase inhibitors may also provide solutions to common fertility problems in the form of letrozole (Femara) and anastrozole (Arimidex). (
  • Following promising data for metastatic breast cancer in terms of efficacy and safety profile, third-generation aromatase inhibitors (AI), anastrozole, letrozole, and exemestane, underwent a full development in early setting. (
  • HealthDay News) - Body mass index (BMI) affects the level of estradiol and estrone sulfate suppression achieved when treating postmenopausal women with estrogen receptor (ER)-positive breast cancer with either of two aromatase inhibitors, anastrozole or letrozole . (
  • At higher BMI, the levels of estrogen were greater for patients receiving treatment with both aromatase inhibitors, and this effect was significant with letrozole. (
  • Letrozole is an Aromatase inhibitor. (
  • When the study ended, 95% of women who had 10 years of aromatase inhibitor therapy (Letrozole) had disease-free survival (meaning they did not develop a recurrence or a new cancer in the other breast), while 91% of women who had 5 years of aromatase inhibitor therapy had disease-free survival at the study endpoint. (
  • I know gynecomastia will be an issue so I also plan on taking the aromatase inhibitor Letrozole. (
  • Advanced breast cancer: diagnosis and treatment ' (NICE clinical guideline 81) recommends that if the disease is not imminently life threatening, or does not need early relief of symptoms because of significant visceral organ involvement, women who are postmenopausal and have hormone-receptor-positive breast cancer should be offered an aromatase inhibitor such as anastrozole or letrozole. (
  • The first such study to be reported was a comparison of the aromatase inhibitor anastrozole (trade name Arimidex) to tamoxifen or to a combination of the two drugs. (
  • In addition to glucocorticoid replacement, the patient was commenced on growth hormone and a third-generation aromatase inhibitor, anastrozole, in an attempt to optimize his growth. (
  • We report a novel approach to improve linear growth by using recombinant human growth hormone (GH) and anastrozole, an aromatase inhibitor (AI), in combination with glucocorticoids in a patient with late-presenting CYP11B1 deficiency with a markedly advanced bone age. (
  • However, as aromatase inhibitors such as 'Arimidex' (anastrozole) have now demonstrated their superiority over tamoxifen in both the adjuvant setting and as first line therapy for advanced breast cancer, the changing treatment paradigm means that the efficacy and tolerability of 'Faslodex' following aromatase inhibitor therapy has become an important question for clinicians and patients alike. (
  • Anastrozole is a third-generation nonsteroidal selective aromatase inhibitor. (
  • The advantages of using aromatase inhibitors over other hormonal agents such as tamoxifen include a decrease in vaginal discharge, a reduced risk of blood clotting and less risk of womb cancer. (
  • Aromatase inhibitors - which work by lowering estrogen levels - were found to be more effective than tamoxifen in reducing deaths among women with ER-positive breast cancer. (
  • In the US, aromatase inhibitors are currently used to treat early-stage breast cancer in postmenopausal women who have been treated with tamoxifen for around 2-3 years. (
  • Previous research suggests aromatase inhibitors are more effective for reducing breast cancer recurrence than tamoxifen, though how they impact survival has been unclear. (
  • The women in the trials had either received no hormonal therapy or had used aromatase inhibitors or tamoxifen for at least 5 years. (
  • Our global collaboration has revealed that the risk of postmenopausal women with the most common form of breast cancer dying of their disease is reduced by 40% by taking 5 years of an aromatase inhibitor - a significantly greater protection than that offered by tamoxifen. (
  • Aromatase inhibitors and tamoxifen are two types of hormonal therapy. (
  • A study found that women diagnosed with early-stage, hormone-receptor-positive breast cancers who were treated with an aromatase inhibitor were 26% more likely to have cardiac problems -- heart attack, heart-related chest pain (angina), or heart failure -- compared to women treated with tamoxifen. (
  • Many postmenopausal women take hormonal therapy -- either an aromatase inhibitor or tamoxifen -- after surgery and other treatments for hormone-receptor-positive, early-stage breast cancer. (
  • In many cases, one hormonal therapy medicine -- tamoxifen or an aromatase inhibitor -- is taken for 5 years. (
  • In other cases, women take tamoxifen for 2 or 3 years and then switch to an aromatase inhibitor until the hormonal therapy has been taken for a total of 5 years. (
  • So you might take tamoxifen for 2 years and an aromatase inhibitor for 3 years. (
  • Five years of an aromatase inhibitor is somewhat better than 5 years of tamoxifen for reducing the risk of recurrence in postmenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer -- about 20% better overall. (
  • Sequential therapy (tamoxifen for 2 to 3 years followed by an aromatase inhibitor) can reduce the risk of recurrence about the same as 5 years of an aromatase inhibitor. (
  • 3.4% of the women treated with 5 years of tamoxifen had a cardiovascular problem compared to 4.2% of the women treated with 5 years of an aromatase inhibitor. (
  • Women who got tamoxifen for 2 to 3 years followed by an aromatase inhibitor had the same risk of cardiovascular problems as women who got 5 years of tamoxifen. (
  • In rare cases, both tamoxifen and the aromatase inhibitors can lead to dangerous blood clots. (
  • This risk is higher with tamoxifen and lower with an aromatase inhibitor. (
  • Both tamoxifen and the aromatase inhibitors have been linked to a small risk of uterine cancer. (
  • This study found that broken bones due to hormonal therapy were 47% more likely in women who got 5 years of an aromatase inhibitor compared to women who got 5 years of tamoxifen. (
  • Research also has shown that hot flashes and night sweats -- called vasomotor symptoms -- are side effects of both tamoxifen and the aromatase inhibitors, though they're more common with tamoxifen. (
  • We are not aware of any studies published on the effect of aromatase inhibitors in dogs with mammary carcinoma, but based on the fact that many of these tumors are estrogen-dependent, express estrogen receptors, and respond to tamoxifen, it is reasonable to believe that aromatase inhibitors should be effective. (
  • Aromatase inhibitors prevent estrogen synthesis, whereas tamoxifen works by blocking the estrogen receptor. (
  • Any differences in the prevalence of hypercholesterolemia or cardiovascular events between the aromatase inhibitors and tamoxifen could be explained by the well-known cardioprotective and lipid-lowering effects of tamoxifen, he said, and not an increased risk from the drugs themselves. (
  • There are no differences between [aromatase inhibitors and tamoxifen] in terms of safety issues or cardiovascular issues. (
  • The aromatase inhibitors are rapidly replacing tamoxifen as the adjuvant treatment of choice for early breast cancer in postmenopausal women, a population with comorbidities like diabetes and hypertension. (
  • But trials that compare aromatase inhibitors with tamoxifen have raised some concerns about whether these medications increase cardiovascular risk. (
  • Dr. Monnier analyzed several trials involving the aromatase inhibitors in comparison with tamoxifen or placebo. (
  • Dr. Dickler said, "When you're comparing an [aromatase inhibitor] to tamoxifen, it's easy to forget that tamoxifen does have lipid-lowering effects. (
  • Dr. Monnier concluded that comparisons of aromatase inhibitors with placebo may be more useful in determining the risks associated with treatment, considering the protective effect of tamoxifen. (
  • There are ongoing trials that will anwer the questions of 2-3 years of tamoxifen followed by an aromatase inhibitor. (
  • Also, there will be information from trials testing aromatase inhibitors following 5 years of tamoxifen. (
  • Recent advances in breast cancer treatment include the advent of aromatase inhibitors (AIs) in the adjuvant setting with better efficacy and toxicity profiles than tamoxifen. (
  • A study published August 22 in the Journal of The National Cancer Institute says that the toxicities associated with aromatase inhibitors (AIs) may explain the lack of overall survival improvement compared with tamoxifen. (
  • Switching from tamoxifen to aromatase inhibitors reduces this toxicity and is likely the best balance between efficacy and toxicity. (
  • Thus, it is conceivable that a late survival advantage with aromatase inhibitors over tamoxifen may also emerge over time. (
  • Tamoxifen has traditionally been preferred over the use of aromatase inhibitors (AIs) in this group. (
  • Professor Jack Cuzick, a Cancer Research UK epidemiologist based at Queen Mary, University of London, said: "This study confirms what we've known for some time - that the aromatase inhibitors are more effective than tamoxifen at delaying the return of breast cancer in postmenopausal women with hormone receptor-positive early breast cancer. (
  • Or, your provider may switch you to another aromatase inhibitor (you may have less pain with a different drug) or recommend tamoxifen [ 90 ]. (
  • Aromatase inhibitors cause a loss of bone density, which leads to higher rates of osteoporosis and bone fractures compared to tamoxifen [ 86 ]. (
  • Although both aromatase inhibitors and tamoxifen can cause menopausal symptoms such as hot flashes, many of their side effects differ (see Figure 5.11 below). (
  • Risk of the most serious cardiovascular events, cardiac ischemia and stroke, were not increased in breast cancer patients taking aromatase inhibitors compared with tamoxifen users. (
  • Few women with invasive breast cancer who are treated with lumpectomy, radiation and five years of tamoxifen would benefit from taking an aromatase inhibitor after tamoxifen. (
  • For this study, we looked at women who were free of cancer after completing all therapy, including five years of tamoxifen, to better define which women would benefit from taking an aromatase inhibitor rather than recommending it for all women. (
  • After looking at all the factors of the women in this retrospective study, we believe the addition of an aromatase inhibitor to the five years of tamoxifen for all patients would result in only a 1 to 2 percent clinical benefit," explained Freedman. (
  • Women with-node positive breast cancer and women aged 60 years or younger would be the ones more likely to benefit from the addition of an aromatase inhibitor after completing the 5 years of tamoxifen. (
  • In this phase II trial, 67 postmenopausal women with advanced breast cancer whose disease had progressed after previous treatment with both tamoxifen and then an aromatase inhibitor were assessed. (
  • Well, tamoxifen causes far less bone loss than the aromatase inhibitors, so it is worth looking into if you might be able to use tamoxifen rather than one of the aromatase inhibitors. (
  • Does anyone know, PLEASE, if there are treatments (Natural) that would work as well as Aromatase Inhibitors and Tamoxifen? (
  • The aromatase inhibitors (AIs) are becoming the preferred treatment over tamoxifen as adjuvant therapy for postmenopausal women with hormone-sensitive early breast cancer. (
  • Biological and clinical effects of aromatase inhibitors in neoadjuvant therapy. (
  • Howell A, Cuzick J (2005) Vascular effects of aromatase inhibitors: data from clinical trials. (
  • Joint pain (arthralgia) and muscle pain (myalgia) are common side effects of aromatase inhibitors [ 85-87 ]. (
  • Adjuvant trials evaluating the effects of aromatase inhibitors or inactivators in early breast cancer. (
  • Patients also need to consider the side effects of aromatase inhibitors and the cost of the drug. (
  • Androstenedione + 3O2 + 3NADPH + 3H+ ⇌ {\displaystyle \rightleftharpoons } Estrone + Formate + 4H2O + 3NADP+ Testosterone + 3O2 + 3NADPH + 3H+ ⇌ {\displaystyle \rightleftharpoons } 17β-estradiol + Formate + 4H2O + 3NADP+ Aromatase is expressed in the gonads, placenta, brain, adipose tissue, bone, and other tissues. (
  • Aromatase is an estrogen synthase that synthesize estrone (E1) and estradiol (E2) from Androstenedione and Testosterone respectively. (
  • Aromatase deficient female cannot synthesize estrone or estradiol in the absence of aromatase. (
  • General reaction for the conversion of testosterone to estradiol catalyzed by aromatase. (
  • Of interest, several clinical and experimental studies on estrogen and/or aromatase deficiency also reinforced the hypothesis of a threshold estradiol level for skeletal sufficiency in the male [ 1 - 4 ]. (
  • A drug that prevents the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. (
  • The study was a randomized trial of high-dose estradiol (10 mg t.i.d., 30 mg total) versus low-dose estradiol (2 mg t.i.d., 6 mg total) in 66 postmenopausal women with acquired resistance to aromatase inhibitors. (
  • In healthy aging men, testosterone levels decline and estradiol levels increase, possibly due to increasing aromatase activity in aging. (
  • People with Klinefelter's syndrome (KS) have four times normal aromatase activity and can develop low testosterone levels and high estradiol levels. (
  • The pituitary gland can produce estradiol locally in several types of endocrine cells, and it is possible that aromatase could be responsible for the maintenance of the population of lactotroph cells and the modulation of the action of central or peripheral regulators. (
  • The involvement of aromatase in the pathogenesis of pituitary tumors, mainly prolactinomas, through the auto-paracrine production of estradiol is reviewed. (
  • We also studied alternative use of multiple exons 1 of its gene and immunolocalization of type I 17β-hydroxysteroid dehydrogenase (HSD), which converts estrone produced by aromatase to estradiol. (
  • Which means that if there is an overabundance of testosterone around, the aromatase enzyme favours the production of estradiol. (
  • To examine the correlation between estrogen suppression and aromatase inhibitors and BMI, Elizabeth Folkerd, PhD, of the Royal Marsden National Health Service Foundation Trust in London, and colleagues evaluated plasma estradiol and estrone sulfate levels with a highly-sensitive radioimmunoassay for 44 postmenopausal women with ER-positive breast cancer. (
  • These are also found in red wine, and the researchers had already shown that these compounds inhibit aromatase, the enzyme that converts testosterone and androstenedione into estradiol. (
  • They put increasing concentrations of the extract in test tubes with aromatase producing cells, and then measured how much estradiol was produced. (
  • An important function of aromatase in the brain is conversion of testosterone secreted from the testis into estradiol. (
  • During fetal development, aromatase converts androgens to estrogens in the placenta, which is the link between the mother's blood supply and the fetus. (
  • A shortage of functional aromatase results in an inability to convert androgens to estrogens before birth and throughout life. (
  • The enzyme aromatase works alongside NADPH (nicotinamide adenine dinucleotide phosphate) to convert male hormones or androgens to estrogens. (
  • The aromatase enzyme catalyzes the conversion of androgens to estrogens in many human tissues. (
  • The aromatase enzyme, a product of the CYP19A1 gene, catalyzes the conversion of androgens to estrogens in many human tissue sites [ 1 - 3 ]. (
  • Aromatase, also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. (
  • In particular, aromatase is responsible for the aromatization of androgens into estrogens. (
  • During pregnancy, the placenta, which is fetal tissue, synthesizes large amounts of the intermediates in the biosynthesis of the estrogens, androstenedione and testosterone, but cannot convert them to estrogens due to the absence of aromatase. (
  • Aromatase is a specific component of the cytochrome P450 enzyme system responsible for the transformation of androgen precursors into estrogens. (
  • The activity of aromatase regulates the concentrations of estrogens with endocrine, paracrine, and autocrine effects on target issues including bone. (
  • These new observations underscore the normal biosynthetic pathway by which estrogens are made in men, via the activity of aromatase (a cytochrome P450 product of the CYP19A1 gene) on circulating androgenic precursors (Figure 1 ). (
  • AROD is a rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. (
  • Because estrogens also promote certain cancers and other diseases, aromatase inhibitors are frequently used to treat those diseases. (
  • Aromatase is a member of the cytochrome P450 superfamily ( EC ), whose function is to aromatize androgens , producing estrogens . (
  • The primary function of aromatase is to produce estrogens by aromatizing androgens. (
  • [4] Aromatase is also a key enzyme in the biosynthesis of estrogens through a process called steroidogenesis. (
  • Aromatase enzyme stimulates the conversion of testosterone and androstenedione into estrogens. (
  • Aromatase P450, the enzyme responsible for the catabolization of aromatizable androgens to estrogens, is expressed in different parts of body, including the pituitary gland. (
  • Recently in situ production of estrogens by aromatase was detected in human bone and cultured osteoblasts and has been proposed to participate in the maintenance of bone mass. (
  • These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens. (
  • To produce estrogens, both male and female bodies produce androgens, specifically testosterone, and use an enzyme called aromatase to convert the testosterone into estrogen. (
  • Aromatase is a crucial enzyme for the biosynthesis of estrogens and is involved in the process of breast carcinogenesis. (
  • Concerns have been raised regarding the effects of environmental estrogens as potential regulators of aromatase expression in human breast cells. (
  • The present study hypothesized that aromatase expression and activity may be elevated by low dose zeranol exposure, providing a source of estrogens that may stimulate cell proliferation. (
  • Origin of breast cancer tissue estrogens and sites of action of aromatase inhibitors and inactivators. (
  • Aromatase plays a critical role in steroidogenesis, catalyzing the conversion of androgenic hormones into estrogens. (
  • Inhibitors of aromatase are used to treat estrogen-dependent breast cancer, as estrogens promote the expression of peptide growth factors responsible for tumorigenesis. (
  • Mutations in the CYP19A1 gene cause aromatase deficiency. (
  • The CYP19A1 gene provides instructions for making an enzyme called aromatase. (
  • CYP19A1 gene mutations that cause aromatase deficiency decrease or eliminate aromatase activity. (
  • This condition is due to mutations in the CYP19A1 gene which encodes aromatase. (
  • Defects in CYP19A1 are the cause of aromatase deficiency (AROD) [MIM:107910]. (
  • In human pulmonary arterial smooth muscle cells, metformin decreased proliferation and decreased estrogen synthesis by decreasing aromatase activity through the PII promoter site of Cyp19a1 . (
  • KLH conjugated synthetic peptide between 221-253 amino acids from the Central region of human Aromatase (CYP19A1). (
  • Since postmenopausal women have small and shrunken ovaries that produce low levels of estrogen, use of aromatase inhibitors may further prevent estrogen production and its stimulation of the tumour growth. (
  • A new study claims a class of hormonal drugs called aromatase inhibitors may significantly reduce the risk of death among postmenopausal women with estrogen receptor-positive breast cancer - the most common form of the disease. (
  • The risks and benefits of adjuvant aromatase inhibitors (AIs) should be weighed carefully, especially in postmenopausal women with early-stage, hormone-receptor positive breast cancer who also have coronary artery disease. (
  • This meta-analysis confirms that an aromatase inhibitor (AI) is not the best therapy for all postmenopausal women with hormone-receptor positive, early-stage, breast cancer. (
  • Aromatase inhibitors (AIs) have quickly become standard treatments for postmenopausal women with estrogen-receptor-positive breast cancer. (
  • Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast cancer patients. (
  • BERLIN, April 18 -- In postmenopausal women with breast cancer, adjuvant treatment with aromatase inhibitors does not raise the risk for cardiovascular events, a researcher said. (
  • Aromatase inhibitors are used as a type of hormone therapy for postmenopausal women who have hormone-dependent breast cancer. (
  • These results indicate that suppression of estrogen formation in postmenopausal women by aromatase inhibitors may be a useful prevention/treatment strategy in these women. (
  • Aromatase inhibitors are only used to treat postmenopausal women (and some premenopausal women also getting ovarian suppression). (
  • These findings indicate the importance of oestrogen actions in DCIS, and aromatase inhibitors might be effective for postmenopausal women with ER-positive DCIS as well as invasive carcinoma. (
  • disease because aromatase inhibitors are the standard hormonal therapy for postmenopausal women. (
  • Important new data from two studies presented at the 27th Annual San Antonio Breast Cancer Symposium (SABCS) in the USA, suggest that 'Faslodex' (fulvestrant) is an effective and well tolerated treatment for postmenopausal women with advanced breast cancer who have experienced disease progression on aromatase inhibitor therapy. (
  • In this phase II trial, 77 postmenopausal women with advanced breast cancer whose disease progressed following treatment with an aromatase inhibitor and, at most, one additional hormonal agent, were assessed. (
  • Vaginal gene expression in aromatase inhibitor-treated women was compared with postmenopausal control women treated with vaginal estrogen therapy. (
  • Background: Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. (
  • HealthDay News - For postmenopausal women with breast cancer, extension of treatment with an aromatase inhibitor to 10 years is associated with improved outcomes, according to a study published online June 5 in the New England Journal of Medicine . (
  • In women who are pregnant with an affected fetus, excess androgens in the placenta pass into the woman's bloodstream, which may cause her to have temporary signs and symptoms of aromatase deficiency. (
  • I didn't realize androgens can be covered by aromatase into estrogen. (
  • The inhibition of oestrogen synthesis is most readily achieved by inhibiting the final step in the pathway of oestrogen biosynthesis, the reaction which transforms androgens into oestrogens by creating an aromatic ring in the steroid molecule (hence the enzyme's trivial name, aromatase). (
  • Aromatase is an enzyme that is required for the conversion of androgens or "male" hormones such as testosterone into estrogen. (
  • They prevent the enzyme aromatase from converting androgens (also known as the male hormones) into estrogen. (
  • Femara and Arimidex work by blocking the enzyme aromatase from converting the androgens or "male" hormones into estrogen in both men and women. (
  • Arimidex inhibits estrogen synthesis by out- competing androgens' ability to bind with aromatase. (
  • appearance: white to light yellow crystal Application: Femara is a type II (non-steroidal) third generation aromatase inhibitor . (
  • Aromatase inhibitors like Femara may be used to stimulate ovulation in women. (
  • Aromatase inhibitors like Femara help female fertility by inducing ovulation. (
  • The purpose of this study is to determine how aromatase inhibitors (AIs) such as Arimidex, Aromasin or Femara affect a woman's oral health and oral health related quality of life. (
  • Aromatase inhibitors like Femara trigger ovulation in women. (
  • Women using aromatase inhibitor, like Femara, showed predictable multiple follicular responses in most cycles. (
  • RORA is the gene for aromatase, an enzyme that converts male to female hormones. (
  • Steroids are composed of four fused rings (labeled A-D). Aromatase converts the ring labeled "A" into an aromatic state. (
  • AIs stop the production of estrogen by blocking the enzyme aromatase, which converts the hormone androgen into estrogen. (
  • then, on other hand, it prevents the aromatization of Testosterone (the pathway by which the enzyme, Aromatase, converts Testosterone into Estrogen). (
  • The enzyme aromatase converts that hormone into estrogen. (
  • It's one of a class of drugs called aromatase inhibitors and prevents the production of estrogen by binding to and shutting down an enzyme called aromatase. (
  • Getting rid of excess body fat is the number one way to reduce your risk of hormone-positive breast cancer because your fat cells can produce estrogen from testosterone using an enzyme called aromatase - hence the use of aromatase inhibitors to block this process. (
  • AEXS is characterized by an estrogen excess due to an increased aromatase activity. (
  • In order to confirm findings from studies such as these, AstraZeneca are undertaking two large-scale international, randomised controlled trials of 'Faslodex' following aromatase inhibitor therapy, known as the EFECT trial (Evaluation of Fulvestrant versus Exemestane Clinical Trial) and the SOFEA trial (Study of 'Faslodex', Exemestane and 'Arimidex'), both of which are expected to confirm the efficacy and tolerability of 'Faslodex' in this important setting. (
  • In this video I wanted to discuss with you whether boron is safe for breast cancer survivors who are taking aromatase inhibitors such as Arimidex. (
  • Arimidex and the other aromatase inhibitors are so effective at preventing the production of estrogen that if you are taking one of these drugs you will be producing virtually no estrogen. (
  • Taking the aromatase inhibitor exemestane (Aromasin) for primary prevention of breast cancer may weaken the bones, researchers found. (
  • Effective Aromatase Inhibitor Exemestane / Aromasin Powder Description: Exemestane is a steroidal Aromatase Inhibitor (AI) that is most commonly known as Aromasin. (
  • Exemestane is an oral steroidal aromatase inhibitor that is used in ER-positive breast cancer in addition to surgery and/or radiation in post-menopausal women. (
  • Phytoestrogens may contribute to decreased cancer risk by the inhibition of aromatase enzyme activity and CYP19 gene expression in human tissues. (
  • However, other studies investigated the influence of phytoestrogens on the human aromatase enzyme where inhibition of aromatase activity has been demonstrated [ 4 , 5 , 8 ]. (
  • Ineffective Inhibition of Aromatase: A Cause for AI Resistance? (
  • The hypoglycemic drug, metformin, is reported to have multiple actions, including the inhibition of aromatase and stimulation of AMP-activated protein kinase. (
  • Inhibition of aromatase using anastrazole is protective in experimental pulmonary hypertension but whether metformin attenuates pulmonary hypertension through this mechanism remains unknown. (
  • Thus, we report for the first time that metformin can reverse pulmonary hypertension through inhibition of aromatase and estrogen synthesis in a manner likely to be mediated by AMP-activated protein kinase. (
  • 13 - 17 Estrogen is synthesized from testosterone through the enzyme aromatase and inhibition of aromatase attenuates experimental PH but only in females. (
  • The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. (
  • In general, phytoestrogens act as aromatase inhibitors by (a) decreasing aromatase gene expression, (b) inhibiting the aromatase enzyme itself, or (c) in some cases acting at both levels of regulation. (
  • I want to keep my estrogen low by inhibiting the aromatase enzyme and keep my dihydrotestosterone low by inhibiting the 5-alpha reductase enzyme. (
  • Aromatase inhibitors lower estrogen levels by preventing the enzyme aromatase - found in fat tissue - from changing other hormones into estrogen. (
  • third generation aromatase inhibitors , used in the treatment of metastatic breast cancer and used as aid in the treatment of early breast cancer. (
  • What's very interesting to me, though, is the anti-aromatase properties. (
  • By using an anti-aromatase, it should, theoretically, allow the levels of free testosterone to build up in my body by overriding the body's ability to maintain homeostasis. (
  • Therefore, our laboratory initiated a research project to investigate anti-aromatase phytochemicals in common vegetables that may lead to the suppression of breast cancer cell proliferation. (
  • When should you use an anti-aromatase? (
  • I have nolva for PCT but I want to know when, if any, is a proper time to take an anti-aromatase? (
  • I read that Nolva and an anti-aromatase can be taken together, for your PCT, to prevent losing any mass or strength gained during the cycle. (
  • Actually, the article mentioned to start the anti-aromatase at the beginning of a cycle and continue through PCT with novla. (
  • However, it still doesn't help me know when I should take an anti-aromatase. (
  • After the second week I will add an anti-aromatase and continue past my nolva for about another 1-2 weeks after I finish my nolva dosing. (
  • Anti-Estrogen or Anti-Aromatase? (
  • Moreover, one or two hydrogen bond acceptor features, hydrophobicity, and steric factors may play crucial roles for anti-aromatase activity. (
  • Ribbon diagram displaying the overall structure of human placental aromatase. (
  • A ribbon diagram displaying the overall structure of the human placental aromatase is shown to the left. (
  • A cloned complementary DNA sequence has been isolated from a human placental cDNA library in the bacteriophage expression vector lambda gt11 after screening with polyclonal antibodies against human placental aromatase-system cytochrome P-450 (P-450Arom). (
  • Our experiments revealed that of the seven vegetable extracts tested, the extract of white button mushroom was the most effective in inhibiting the activity of human placental aromatase ( 4 ). (
  • The PromoKine Aromatase Activity Assay Kit enables rapid measurement of native or recombinant aromatase activity in biological samples such as placental microsomes. (
  • Aromatase deficiency is a condition characterized by reduced levels of the female sex hormone estrogen and increased levels of the male sex hormone testosterone. (
  • There are other features associated with aromatase deficiency that can affect both males and females. (
  • Males and females with aromatase deficiency can have abnormally high blood sugar (hyperglycemia) because the body does not respond correctly to the hormone insulin . (
  • Women who are pregnant with fetuses that have aromatase deficiency often experience mild symptoms of the disorder even though they themselves do not have the disorder. (
  • In affected individuals, these abnormal hormone levels lead to impaired female sexual development, unusual bone growth, insulin resistance, and other signs and symptoms of aromatase deficiency. (
  • Aromatase deficiency, a rare syndrome: case report. (
  • Aromatase deficiency is a very rare condition characterised by the extremely low or absence of the enzyme aromatase activity in the body. (
  • During gestation, a baby with Aromatase Deficiency can cause a mother to become virilised by causing the deepening of the voice, cystic acne, cliteromegaly, and hirsutism. (
  • Aromatase deficiency may be comorbid with Autism through their mutual relationship with RORA deficiency. (
  • Thus, RORA deficiency is linked to aromatase deficiency, which in turn can lead to elevated testosterone levels, a proposed risk factor for autism. (
  • Aromatase has been studied regarding the effects of excess and deficiency by testing mouse models of these states. (
  • Men with aromatase deficiency due to mutation are very rare. (
  • In fact, an experimental animal model of estrogen deficiency was generated in mice by targeted disruption of the aromatase gene ( 14 - 16 ), and the roles of estrogen in reproductive behaviors were extensively investigated ( 17 - 19 ). (
  • Fifty percent of women taking aromatase inhibitors reported musculoskeletal pain, and up to 30% reported fatigue. (
  • About 46 percent of women taking aromatase inhibitors have joint pain and about 15 percent have muscle pain [ 85-87 ]. (
  • Aromatase inhibitor use has been shown to reduce the risk of breast cancer recurrence. (
  • Aromatase inhibitors aren't commonly used to reduce recurrence risk in premenopausal women. (
  • Still, when the researchers looked at just the 309 women older than age 50 diagnosed with estrogen-receptor-positive disease who were treated with an aromatase inhibitor after surgery, they found that smoking increased the risk of recurrence as well as the risk of dying from breast cancer. (
  • Smokers who were treated with aromatase inhibitors had a three times higher risk of recurrence of breast cancer compared with the non-smokers who got the same treatment," said Helena Jernström, associate professor at Lund University and lead author of the study. (
  • Loss of bone density and fractures are known risks of aromatase inhibitors in breast cancer survivors taking the drugs to reduce recurrence risk, Jane A. Cauley, DrPH, of the University of Pittsburgh, noted in an accompanying editorial. (
  • Still, this treatment is not curative in advanced breast cancer, but many studies were then started to test aromatase inhibitors in early stage breast cancer in hopes that it could lower recurrence and mortality in early stage breast cancer. (
  • A new study looks at whether extending one type of hormonal therapy, known as aromatase inhibitor therapy, to 10 years lowers recurrence rates even more for these women. (
  • Whether patients will benefit (lower risk of recurrence or new breast cancer in the other breast) if they stay on aromatase inhibitor therapy for 10 years rather than the standard 5 years. (
  • The risk of disease recurrence and contralateral breast cancer was significantly lower among women who continued aromatase inhibitor for 10 years than among women who received placebo after the initial 5 years of aromatase-inhibitor therapy," the authors write. (
  • The gene for aromatase is expressed in many tissues (including testis), and hormone production controls male fertility. (
  • When the researchers looked at why that happened, they saw that GSE sabotages two transcription factors that the cell needs to read the gene for aromatase. (
  • The aim of the study is to establish the short-term efficacy and safety of aromatase inhibition in restoring and maintaining eugonadism in hypogonadotrophic hypogonadal men. (
  • The induced expression of aromatase apparently elevates local estrogen levels enough to interfere with apoptotic pathways, thereby decreasing secondary degeneration and ultimately lessening the extent of damage. (
  • Therefore, abnormal expression of aromatase, the enzyme responsible for the synthesis of estrogen, in breast cancer cells and/or surrounding adipose stromal cells may have a significant influence on tumor development and growth in breast cancer patients. (
  • The ArKO/bsArTG mice exhibited significant restoration of impaired behaviors, suggesting that brain-restricted expression of aromatase is sufficient for the display of reproductive behavior. (
  • Thus, expression of aromatase in the brain is suggested to be essential for reproductive behavior in mice. (
  • Kagawa N. Efficient expression of human aromatase (CYP19) in E. coli. (
  • The study involved a prospective cohort of 290 women starting on aromatase inhibitors, who had baseline Vitamin D levels measured. (
  • The goal of this article was to study the effect of the aromatase enzyme in human testes, the effects of high and low hormone levels on the testes, as well as the location of aromatase in testes. (
  • Fadrozole is a nonsteroidal aromatase inhibitor exhibiting a very potent and selective inhibitory effect of the aromatase enzyme system in vivo and estrogen biosynthesis in vivo. (
  • Mechanism of the chemical reaction catalyzed by the aromatase enzyme. (
  • Strong aromatase immunoreactivity and mRNA hybridization as well as type I 17β-HSD immunoreactivity were detected in lining cells, osteoblasts, chondrocytes of articular cartilage, and adipocytes adjacent to bone trabeculae in all the cases examined. (
  • Amounts of aromatase mRNA varied greatly among the subjects (11.25 ± 9.77, 0.61-42.84 attomol/ng of total RNA). (
  • Changes in the levels of adipose stromal cell RNA that hybridized to the cDNA insert were associated with comparable changes in the levels of translatable cytochrome P-450Arom mRNA and aromatase system activity. (
  • These findings are indicative that lambda hAROM1 contains DNA sequences complementary to human cytochrome P-450Arom mRNA and are suggestive that regulatory factors affect aromatase activity by altering the transcriptional activity of the cytochrome P-450Arom gene. (
  • The results demonstrated that low dose zeranol (2‑50 nM) was able to significantly promote cell proliferation, aromatase mRNA expression, aromatase activity and estrogen production in primary cultured human breast preadipocytes, thus suggesting that zeranol may act as an aromatase activator. (
  • Knockdown of ARP-1 significantly suppressed the increase in aromatase mRNA observed in cultured neurons. (
  • Aromatase inhibitors are a class of hormonal agents that form part of the therapy for some types of breast cancer . (
  • But their study suggests another class of hormonal drugs - called aromatase inhibitors - may be more effective. (
  • A study suggests that smoking makes a class of hormonal therapy medicines, the aromatase inhibitors, much less effective. (
  • The data from these two studies represent an important finding since they suggest that patients with advanced breast cancer who have progressed on aromatase inhibitor therapy have an additional effective and well tolerated hormonal treatment option at their disposal, which further delays the need to use chemotherapy. (
  • These new data therefore represent an important development that will be eagerly welcomed by the oncology community, since they suggest that women who have received prior non-steroidal aromatase inhibitor therapy now have an additional effective and well-tolerated hormonal therapy with which to fight their disease, extending the benefits of hormonal therapy and delaying the need for the more aggressive chemotherapy. (
  • Moreover, with aging, individual differences in aromatase activity may significantly affect bone loss and fracture risk in men. (
  • The treatment with aromatase inhibitors worked significantly better in the non-smoking patients," she continued. (
  • the spine, hip, neck, and other sites also showed significantly worse bone loss with the aromatase inhibitor, despite the calcium and vitamin D supplementation used in the trial. (
  • Spine, hip, neck, and other sites showed significantly worse bone loss with the aromatase inhibitor as well, despite the calcium and vitamin D supplementation used in the trial, the group reported online in the Lancet Oncology . (
  • This study demonstrates the potential of aromatase inhibitors to significantly and rapidly reduce disease severity and pain, offering women a new and more effective way of suppressing endometriosis with fewer side effects," explains Dr. Bulun. (
  • A large clinical trial, which involved a total of 226 patients from 11 cancer centers, has found that acupuncture can significantly reduce the troublesome joint pain caused by the aromatase inhibitors. (
  • Recent clinical trials have shown aromatase inhibitors to be effective in the treatment of hormone-responsive breast cancer and to significantly prevent contralateral cancers ( 1 - 3 ). (
  • Among the patients using oral contraceptives in extended regimens, the relative decrease in both aromatase and Cox-2 expression was significantly greater in amenorrheic patients compared with those who were experiencing breakthrough bleeding. (
  • Here we describe the considerable consensus and some interesting differences in knowledge gained from studies conducted on diverse animal models, experimental paradigms and preparations towards understanding the neuroprotective actions of brain aromatase. (
  • Over relatively long time periods (days to months), brain aromatase activity (AA), and transcription are markedly (four- to sixfold) increased by genomic actions of sex steroids. (
  • We analyzed the brain-specific promoter to elucidate the control mechanisms of brain aromatase expression that may be highly involved in sexual differentiation of the brain. (
  • Venturini M, Del Mastro L (2006) Safety of adjuvant aromatase inhibitor therapy. (
  • Breast cancer survivors who are prescribed an adjuvant aromatase inhibitor (AI) want ongoing communication with their oncology clinician about the potential for arthralgia and how these joint adverse effects can be managed through regular physical activity, a study published online ahead of print in the journal Supportive Care in Cancer has shown. (
  • It varies from species to species whether it is the aromatase protein that has different activity at different temperatures or whether the amount of transcription undergone by the aromatase gene is what is temperature-sensitive, but in either case, differential development is observed at different temperatures. (
  • The first section covers general knowledge about aromatase inhibitors, including regulation of aromatase genes, and structure and function of aromatase protein. (
  • In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women. (
  • To analyze the effects of ARP-1 on transcriptional regulation of the brain-specific aromatase promoter, a luciferase reporter plasmid driven by the brain-specific promoter was transfected into CV-1 cells together with a plasmid expressing ARP-1 protein. (
  • Crystallographic structure of the human aromatase cytochrome P450 (rainbow colored cartoon, N-terminus = blue, C-terminus = red) in complex with the cofactor protoporphyrin IX (top) and the substrate androstenedione (bottom) depicted as stick diagrams (carbon = white, oxygen = red, nitrogen = blue, iron = orange). (
  • Aromatase ( EC ) belongs to the Cytochrome P450 family (CYP). (
  • During aromatization reactions, aromatase forms an electron-transfer complex with its partner, NADPH-cytochrome P450 reductase . (
  • Aromatase (CYP19A, EC is a member of the cytochrome P450 monooxidase (CYP) family of microsomal xenobiotic metabolism enzymes. (
  • I. To determine whether other SNPs in cytochrome P450 enzymes (CYP), glucuronosyltransferases (UGT), Vitamin D, serotonin and other receptors are associated with discontinuation of treatment due to the development of severe aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). (
  • Patients, dental professionals and medical oncologists will benefit from a greater understanding of the best oral care follow up practices of breast cancer survivors using aromatase inhibitors. (
  • In this latest video, Lara talks about whether boron is safe for breast cancer survivors who are taking aromatase inhibitors. (
  • Because breast cancer survivors receiving aromatase inhibitors often experience adverse events of joint pain, stiffness, or achiness, researchers sought to assess survivors' knowledge regarding potential joint pain side effects and how both adverse events and their management through moderate physical activity could be discussed during routine visits with an oncology clinician. (
  • Using testosterone as starting material, a new short synthesis of an aromatase inhibitor, 4-OHA, has been achieved through hydroboration/oxidation followed by a Swern type oxidation and epimerization. (
  • In songbirds and mammals, the brain itself appears to be the site of injury-induced estrogen synthesis via the rapid transcription and translation of aromatase (estrogen synthase) in astroglia. (
  • however, if aromatase is nonfunctional due to a mutation, estrogen synthesis cannot occur. (
  • The present study reports on the synthesis of pituitary aromatase, its regulation by gonadal steroids, and the physiological roles of aromatase on pituitary endocrine cells. (
  • It may offer greater selectivity compared with other aromatase inhibitors, being without any intrinsic endocrine effects and with no apparent effect on the synthesis of adrenal steroids. (
  • The investigators behind a recent clinical trial testing acupuncture to treat joint pain caused by aromatase inhibitors used to treat breast cancer are spinning it as a positive study. (
  • Explain to interested patients that this study found that aromatase inhibitors do not increase the risk for hypercholesterolemia or cardiovascular events. (
  • The study also found that aromatase inhibitors produced higher clinical pregnancy rates and more frequent ovulation than Clomid -the number one form of treatment used to help women ovulate. (
  • However, gaps in our knowledge include issues about the cell-specific regulation of aromatase expression, steroidal influences of aromatization distinct from estrogen formation, and questions about the role of constitutive aromatase in neuroprotection. (
  • Safe Steroidal Aromatase Inhibitor Formestane (Lentaron) Powder Description: Formestane is classified as a selective irreversible steroidal aromatase inhibitor . (
  • CGS 20267 is a new non-steroidal compound which potently inhibits aromatase in vitro (IC50 of 11.5 nM) and in vivo (ED50 of 1-3 μg/kg p.o. (
  • Chemical structures of androstenedione and some steroidal aromatase inactivators. (
  • Ligand- and Structure-Based Drug Design of Non-Steroidal Aromatase Inhibitors (NSAIs) in Breast Cancer. (
  • Patients with early-stage breast cancer treated with aromatase inhibitors often experience adverse events that lead to discontinuation. (
  • Whereas these results suggest that these two compounds bind to the active site of aromatase, the inhibition kinetic analysis indicates that they are noncompetitive inhibitors with respect to androstenedione. (
  • Discontinuation and nonadherence were higher among breast cancer patients taking brand name aromatase inhibitors (BAIs) vs generic AIs (GAIs), according to a new study published October 27 in the JNCI: Journal of the National Cancer Institute. (
  • When Are Aromatase Inhibitors Wrong for Breast Cancer Patients? (
  • The 2012 meeing of the Amercian Society of Clinical Oncologists included yet another study demonstrating the benefits of Vitamin D3 in breast cancer patients taking aromatase inhibitors. (
  • Clinically relevant musculoskeletal symptoms develop in women treated with aromatase inhibitors, leading to treatment discontinuation in a substantial percentage of these patients. (
  • To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. (
  • PHILADELPHIA - Use of electroacupuncture (EA) - a form of acupuncture where a small electric current is passed between pairs of acupuncture needles - produces significant improvements in fatigue, anxiety and depression in as little as eight weeks for early stage breast cancer patients experiencing joint pain related to the use of aromatase inhibitors (AIs) to treat breast cancer. (
  • Whereas the first aromatase inhibitors to be used therapeutically could be shown to produce drug-induced inhibition of the enzyme and therapeutic benefits in patients with breast cancer, they were not particularly potent and lacked specificity. (
  • In a multicenter study, researchers sought to determine if acupuncture effectively relieved aromatase inhibitor-related joint pain in patients with breast cancer. (
  • The presence of aromatase and cyclooxygenase-2 (Cox-2) expression was investigated in the endometrium of patients with idiopathic menorrhagia or adenomyosis. (
  • Aromatase expression was detected by immunohistochemistry in the endometrial glands and stroma of patients with idiopathic menorrhagia or adenomyosis. (
  • many environmental chemicals may influence aromatase activity and thereby disrupt endocrine function. (
  • Women with node-positive breast cancer receive extended therapy, including an aromatase inhibitor (AI), for up to a total of 10 years of adjuvant endocrine treatment. (
  • Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. (
  • However, the significance of presurgical aromatase inhibitor treatment remains unclear. (
  • Clinical and experimental evidences clearly indicate that aromatase activity and estrogen production are necessary for longitudinal bone growth, the attainment of peak bone mass, pubertal growth spurt, epiphyseal closure, and normal bone remodeling in young individuals. (
  • White button mushrooms ( Agaricus bisporous ) are a potential breast cancer chemopreventive agent, as they suppress aromatase activity and estrogen biosynthesis. (
  • The effects of zeranol on cell proliferation were measured using the MTS assay, aromatase expression levels were determined by immunocytochemical staining and reverse transcription‑polymerase chain reaction, and aromatase enzyme activity and estrogen production were analyzed using corresponding assay kits. (
  • Compared with women who had not received hormone therapy, those who received aromatase inhibitors were 40% less likely to die from breast cancer in the 10 years after treatment initiation. (
  • Aromatase activity is decreased by prolactin, anti-Müllerian hormone, and the common herbicide glyphosate. (
  • The results suggest that potent specific aromatase inhibitors will be valuable in treating hormone-dependent cancers. (
  • Newswise - Boston, MA- Aromatase inhibitors, when used for up to three years in combination with growth hormone, may effectively and safely help very short adolescent boys grow taller, new research suggests. (
  • This action is done by blocking the aromatase enzyme by turning the hormone, androgen, into small amounts of estrogen. (
  • Aromatase inhibitors thus work by decreasing the amount of testosterone that is converted into estrogen, thus balancing hormone levels. (
  • This patient is only the second reported case of the use of an aromatase inhibitor in combination with growth hormone to optimize height in 11β-hydroxylase-deficient CAH. (
  • Aromatase inhibitors can be used as treatment after surgery for most post-menopausal women who have hormone-receptor positive tumours - which account for around 60 per cent of all breast cancers. (
  • But these results further support the use of aromatase inhibitors as the first line treatment for post-menopausal women with hormone-sensitive breast cancer. (
  • By lowering the production of estrogen, aromatase inhibitors allow for the production of the luteinising hormone (LH) and follicle-stimulating hormone (FSH) , which play important roles in ovulation. (
  • These findings suggest that a number of varieties of mushroom possess inhibitory effects on aromatase activity. (
  • Here we report the first practical application of this method in the screening of molecular entities of therapeutic interest, with human aromatase inhibitory activity as the case study. (
  • We developed an ensemble classification model based on the two-dimensional (2D) DFT MIA-QSAR descriptors, with which we screened the NCI Diversity Set V (1593 compounds) and obtained 34 chemical compounds with possible aromatase inhibitory activity. (
  • The undesirable side effects in current AIs have called for continued pursuit for novel candidates with aromatase inhibitory properties. (
  • This study explores the chemical space of all known AIs as a function of their physicochemical properties by means of univariate (i.e., statistical and histogram analysis) and multivariate (i.e., decision tree and principal component analysis) approaches in order to understand the origins of aromatase inhibitory activity. (