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Estrogen Receptor alpha: 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.Receptors, Estrogen: 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.Estrogen Receptor beta: 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.Estrogens: 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.Estradiol: 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.Selective Estrogen Receptor Modulators: 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)Breast Neoplasms: Tumors or cancer of the human BREAST.Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.Estrogen Receptor Modulators: 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.Tamoxifen: 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.Receptors, Progesterone: 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.Ovariectomy: The surgical removal of one or both ovaries.Uterus: The hollow thick-walled muscular organ in the female PELVIS. It consists of the fundus (the body) which is the site of EMBRYO IMPLANTATION and FETAL DEVELOPMENT. Beyond the isthmus at the perineal end of fundus, is CERVIX UTERI (the neck) opening into VAGINA. Beyond the isthmi at the upper abdominal end of fundus, are the FALLOPIAN TUBES.Cell Line, Tumor: A cell line derived from cultured tumor cells.Estrogens, Non-Steroidal: Non-steroidal compounds with estrogenic activity.Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.Phytoestrogens: PLANT EXTRACTS and compounds, primarily ISOFLAVONES, that mimic or modulate endogenous estrogens, usually by binding to ESTROGEN RECEPTORS.RNA, Messenger: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Estrogens, Conjugated (USP): A pharmaceutical preparation containing a mixture of water-soluble, conjugated estrogens derived wholly or in part from URINE of pregnant mares or synthetically from ESTRONE and EQUILIN. It contains a sodium-salt mixture of estrone sulfate (52-62%) and equilin sulfate (22-30%) with a total of the two between 80-88%. Other concomitant conjugates include 17-alpha-dihydroequilin, 17-alpha-estradiol, and 17-beta-dihydroequilin. The potency of the preparation is expressed in terms of an equivalent quantity of sodium estrone sulfate.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Aromatase: An enzyme that catalyzes the desaturation (aromatization) of the ring A of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the CYP19 gene, and functions in complex with NADPH-FERRIHEMOPROTEIN REDUCTASE in the cytochrome P-450 system.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Promoter Regions, Genetic: 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.Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Antineoplastic Agents, Hormonal: 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)Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Reverse Transcriptase Polymerase Chain Reaction: 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.Nuclear Receptor Coactivator 1: A nuclear receptor coactivator with specificity for ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and THYROID HORMONE RECEPTORS. It contains a histone acetyltransferase activity that may play a role in the transcriptional activation of chromatin regions.Diethylstilbestrol: A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)Nuclear Receptor Coactivator 2: A transcription factor that partners with ligand bound GLUCOCORTICOID RECEPTORS and ESTROGEN RECEPTORS to stimulate GENETIC TRANSCRIPTION. It plays an important role in FERTILITY as well as in METABOLISM of LIPIDS.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Estradiol Congeners: Steroidal compounds related to ESTRADIOL, the major mammalian female sex hormone. Estradiol congeners include important estradiol precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with estrogenic activities.Neoplasms, Hormone-Dependent: 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.MCF-7 Cells: An estrogen responsive cell line derived from a patient with metastatic human breast ADENOCARCINOMA (at the Michigan Cancer Foundation.)Tumor Cells, Cultured: 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.Phenols: Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.Blotting, Western: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Molecular Sequence Data: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.PPAR alpha: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Receptors, Androgen: 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.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Receptor Cross-Talk: The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.Interleukin-13 Receptor alpha2 Subunit: An interleukin-13 receptor subunit that is closely-related to the INTERLEUKIN-13 RECEPTOR ALPHA1 SUBUNIT. The receptor is found as a monomeric protein and has been considered to be a decoy receptor for interleukin-13 due the fact that it lacks cytoplasmic signaling domains.Methoxychlor: An insecticide. Methoxychlor has estrogenic effects in mammals, among other effects.Ethinyl Estradiol: A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Mice, Inbred C57BLNuclear Receptor Coactivator 3: A nuclear receptor coactivator with specificity for ESTROGEN RECEPTORS and PROGESTERONE RECEPTORS. It contains a histone acetyltransferase activity that may play a role in CHROMATIN REMODELING during the process of nuclear receptor-induced transcription. The coactivator has been found at elevated levels in certain HORMONE-DEPENDENT NEOPLASMS such as those found in BREAST CANCER.Benzhydryl Compounds: Compounds which contain the methyl radical substituted with two benzene rings. Permitted are any substituents, but ring fusion to any of the benzene rings is not allowed.Nuclear Receptor Coactivators: Proteins that enhance gene expression when associated with ligand bound activated NUCLEAR RECEPTORS. The coactivators may act through an enzymatic process that affects the rate of transcription or the structure of chromatin. Alternatively nuclear receptor coactivators can function as adaptor proteins that bring nuclear receptors into close proximity with transcriptional complexes.Retinoid X Receptor alpha: A nuclear transcription factor. Heterodimerization with PPAR GAMMA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES.Estrogens, Catechol: 2- or 4-Hydroxyestrogens. Substances that are physiologically active in mammals, especially in the control of gonadotropin secretion. Physiological activity can be ascribed to either an estrogenic action or interaction with the catecholaminergic system.Endocrine Disruptors: 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.Interleukin-13 Receptor alpha1 Subunit: An interleukin receptor subunit with specificity for INTERLEUKIN-13. It dimerizes with the INTERLEUKIN-4 RECEPTOR ALPHA SUBUNIT to form the TYPE II INTERLEUKIN-4 RECEPTOR which has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13. Signaling of this receptor subunit occurs through the interaction of its cytoplasmic domain with JANUS KINASES such as the TYK2 KINASE.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cells, Cultured: 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.Chromatin Immunoprecipitation: A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.Estrous Cycle: The period of cyclic physiological and behavior changes in non-primate female mammals that exhibit ESTRUS. The estrous cycle generally consists of 4 or 5 distinct periods corresponding to the endocrine status (PROESTRUS; ESTRUS; METESTRUS; DIESTRUS; and ANESTRUS).Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Postmenopause: The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Receptors, Retinoic Acid: Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Progesterone: 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.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Thyroid Hormone Receptors alpha: High affinity receptors for THYROID HORMONES, especially TRIIODOTHYRONINE. These receptors are usually found in the nucleus where they regulate DNA transcription. They are encoded by the THRA gene (also known as NR1A1, THRA1, ERBA or ERBA1 gene) as several isoforms produced by alternative splicing.Receptor, erbB-2: A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Vitellogenins: 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.Histone Acetyltransferases: Enzymes that catalyze acyl group transfer from ACETYL-CoA to HISTONES forming CoA and acetyl-histones.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Breast: 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.Luciferases: Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Ovary: 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.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Aromatase Inhibitors: Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.Isoflavones: 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.Hepatocyte Nuclear Factor 3-alpha: A forkhead transcription factor that is an essential activator of GLUCAGON gene expression.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Mammary Glands, Animal: MAMMARY GLANDS in the non-human MAMMALS.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Sex Characteristics: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Endometrial Neoplasms: Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Endometrium: 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.Chlordecone: A highly chlorinated polycyclic hydrocarbon insecticide whose large number of chlorine atoms makes it resistant to degradation. It has been shown to be toxic to mammals and causes abnormal cellular changes in laboratory animals.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Receptors, Estradiol: Cytoplasmic proteins that bind estradiol, migrate to the nucleus, and regulate DNA transcription.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Mammary Neoplasms, Experimental: Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Carcinoma, Ductal, Breast: An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST.Testosterone: 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.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Estriol: A hydroxylated metabolite of ESTRADIOL or ESTRONE that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During PREGNANCY, a large amount of estriol is produced by the PLACENTA. Isomers with inversion of the hydroxyl group or groups are called epiestriol.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Interleukin-4 Receptor alpha Subunit: A receptor subunit that is a component of the TYPE I INTERLEUKIN-4 RECEPTOR and the TYPE II INTERLEUKIN-4 RECEPTOR. It signals through interaction of its cytoplasmic domain with JANUS KINASES such as JANUS KINASE 1.Hydroxytestosterones: 17 beta-Hydroxy-4-androsten-3-ones. Testosterone derivatives formed by the substitution of one or more hydroxyl groups in any position.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Nuclear Receptor Co-Repressor 1: A nuclear protein that regulates the expression of genes involved in a diverse array of processes related to metabolism and reproduction. The protein contains three nuclear receptor interaction domains and three repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 2.Estrone: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Organ Size: The measurement of an organ in volume, mass, or heaviness.Testis: 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.Hypothalamus: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Propionates: Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Ki-67 Antigen: A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.Preoptic Area: Region of hypothalamus between the ANTERIOR COMMISSURE and OPTIC CHIASM.Menopause: The last menstrual period. Permanent cessation of menses (MENSTRUATION) is usually defined after 6 to 12 months of AMENORRHEA in a woman over 45 years of age. In the United States, menopause generally occurs in women between 48 and 55 years of age.Gonadal Steroid Hormones: 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.Sapogenins: The aglucon moiety of a saponin molecule. It may be triterpenoid or steroid, usually spirostan, in nature.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Interleukin-5 Receptor alpha Subunit: A low affinity interleukin-5 receptor subunit that combines with the CYTOKINE RECEPTOR COMMON BETA SUBUNIT to form a high affinity receptor for INTERLEUKIN-5. Several isoforms of the interleukin-5 receptor alpha subunit exist due to multiple ALTERNATIVE SPLICING.Receptors, Steroid: Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Dihydrotestosterone: A potent androgenic metabolite of TESTOSTERONE. It is produced by the action of the enzyme 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE.Interleukin-11 Receptor alpha Subunit: A low affinity interleukin-11 receptor subunit that combines with the CYTOKINE RECEPTOR GP130 to form a high affinity receptor for INTERLEUKIN-11. Multiple isoforms of this protein exist due to ALTERNATIVE SPLICING of its MRNA.alpha7 Nicotinic Acetylcholine Receptor: A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Electrophoretic Mobility Shift Assay: An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.Plant Preparations: Material prepared from plants.Luciferases, Renilla: Luciferases from RENILLA that oxidizes certain LUMINESCENT AGENTS to cause emission of PHOTONS.Nafoxidine: An estrogen antagonist that has been used in the treatment of breast cancer.Ejaculatory Ducts: Paired ducts in the human male through which semen is ejaculated into the urethra.Sp1 Transcription Factor: Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES.Kinetics: The rate dynamics in chemical or physical systems.Retinoid X Receptors: A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Kisspeptins: Intercellular signaling peptides that were originally characterized by their ability to suppress NEOPLASM METASTASIS. Kisspeptins have since been found to play an important role in the neuroendocrine regulation of REPRODUCTION.Androgens: 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.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Androstenediol: An intermediate in TESTOSTERONE biosynthesis, found in the TESTIS or the ADRENAL GLANDS. Androstenediol, derived from DEHYDROEPIANDROSTERONE by the reduction of the 17-keto group (17-HYDROXYSTEROID DEHYDROGENASES), is converted to TESTOSTERONE by the oxidation of the 3-beta hydroxyl group to a 3-keto group (3-HYDROXYSTEROID DEHYDROGENASES).Premenopause: The period before MENOPAUSE. In premenopausal women, the climacteric transition from full sexual maturity to cessation of ovarian cycle takes place between the age of late thirty and early fifty.Hypospadias: A birth defect due to malformation of the URETHRA in which the urethral opening is below its normal location. In the male, the malformed urethra generally opens on the ventral surface of the PENIS or on the PERINEUM. In the female, the malformed urethral opening is in the VAGINA.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Pituitary Gland: A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Orchiectomy: The surgical removal of one or both testicles.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Mediator Complex Subunit 1: A mediator complex subunit that is believed to play a key role in the coactivation of nuclear receptor-activated transcription by the mediator complex. It interacts with a variety of nuclear receptors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; VITAMIN D RECEPTORS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; ESTROGEN RECEPTORS; and GLUCOCORTICOID RECEPTORS.Transforming Growth Factor alpha: An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.Animals, Newborn: Refers to animals in the period of time just after birth.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Integrin alpha6: An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Rete Testis: The network of channels formed at the termination of the straight SEMINIFEROUS TUBULES in the mediastinum testis. Rete testis channels drain into the efferent ductules that pass into the caput EPIDIDYMIS.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Charcoal: An amorphous form of carbon prepared from the incomplete combustion of animal or vegetable matter, e.g., wood. The activated form of charcoal is used in the treatment of poisoning. (Grant & Hackh's Chemical Dictionary, 5th ed)Mammary Neoplasms, Animal: Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.