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.Receptors, Estradiol: Cytoplasmic proteins that bind estradiol, migrate to the nucleus, and regulate DNA transcription.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.Ovariectomy: The surgical removal of one or both ovaries.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.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.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.Estradiol Antagonists: Compounds which inhibit or antagonize the biosynthesis or action of estradiol.Estradiol Dehydrogenases: 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 1.1.1.62Estradiol 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.Luteinizing Hormone: 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.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.Follicle Stimulating Hormone: 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.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.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.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.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.Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as ANDROGEN-BINDING PROTEIN. They differ by their sites of synthesis and post-translational oligosaccharide modifications.Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.Drug Implants: Small containers or pellets of a solid drug implanted in the body to achieve sustained release of the drug.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.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.Ovarian Follicle: 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.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.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.Gonadotropin-Releasing Hormone: A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.Androstenedione: 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.Castration: Surgical removal or artificial destruction of gonads.Estrus: The period in the ESTROUS CYCLE associated with maximum sexual receptivity and fertility in non-primate female mammals.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).Ovulation: The discharge of an OVUM from a rupturing follicle in the OVARY.Menstrual Cycle: The period from onset of one menstrual bleeding (MENSTRUATION) to the next in an ovulating woman or female primate. The menstrual cycle is regulated by endocrine interactions of the HYPOTHALAMUS; the PITUITARY GLAND; the ovaries; and the genital tract. The menstrual cycle is divided by OVULATION into two phases. Based on the endocrine status of the OVARY, there is a FOLLICULAR PHASE and a LUTEAL PHASE. Based on the response in the ENDOMETRIUM, the menstrual cycle is divided into a proliferative and a secretory phase.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.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.Dihydrotestosterone: A potent androgenic metabolite of TESTOSTERONE. It is produced by the action of the enzyme 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Follicular Fluid: 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.Follicular Phase: 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.Prolactin: A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate.Steroids: 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)17-Hydroxysteroid Dehydrogenases: A class of enzymes that catalyzes the oxidation of 17-hydroxysteroids to 17-ketosteroids. EC 1.1.-.Postmenopause: The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life.Trenbolone Acetate: An anabolic steroid used mainly as an anabolic agent in veterinary practice.Inhibins: 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, respectivelyRadioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects.Gonadotropins: 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.Granulosa Cells: 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).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.Breast Neoplasms: Tumors or cancer of the human BREAST.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.Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, DYSPAREUNIA, and progressive development of OSTEOPOROSIS. This may also include the use of progestational agents in combination therapy.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.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)Sexual Maturation: Achievement of full sexual capacity in animals and in humans.Orchiectomy: The surgical removal of one or both testicles.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Preoptic Area: Region of hypothalamus between the ANTERIOR COMMISSURE and OPTIC CHIASM.Chorionic Gonadotropin: 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).Aromatase Inhibitors: Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.Diestrus: A phase of the ESTROUS CYCLES that follows METESTRUS. Diestrus is a period of sexual quiescence separating phases of ESTRUS in polyestrous animals.Sexual Behavior, Animal: Sexual activities of animals.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.Luteal Phase: The period in the MENSTRUAL CYCLE that follows OVULATION, characterized by the development of CORPUS LUTEUM, increase in PROGESTERONE production by the OVARY and secretion by the glandular epithelium of the ENDOMETRIUM. The luteal phase begins with ovulation and ends with the onset of MENSTRUATION.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.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.Progestins: Compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE. Primary actions of progestins, including natural and synthetic steroids, are on the UTERUS and the MAMMARY GLAND in preparation for and in maintenance of PREGNANCY.Estrogens, Non-Steroidal: Non-steroidal compounds with estrogenic activity.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.Organ Size: The measurement of an organ in volume, mass, or heaviness.Ovulation Induction: Techniques for the artifical induction of ovulation, the rupture of the follicle and release of the ovum.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.Dehydroepiandrosterone: 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.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.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.Nafoxidine: An estrogen antagonist that has been used in the treatment of breast cancer.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Ventromedial Hypothalamic Nucleus: A nucleus of the middle hypothalamus, the largest cell group of the tuberal region with small-to-medium size cells.Promegestone: A synthetic progestin which is useful for the study of progestin distribution and progestin tissue receptors, as it is not bound by transcortin and binds to progesterone receptors with a higher association constant than progesterone.Progesterone Congeners: Steroidal compounds related to PROGESTERONE, the major mammalian progestational hormone. Progesterone congeners include important progesterone precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with progestational activities.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.Corpus Luteum: The yellow body derived from the ruptured OVARIAN FOLLICLE after OVULATION. The process of corpus luteum formation, LUTEINIZATION, is regulated by LUTEINIZING HORMONE.Proestrus: A phase of the ESTROUS CYCLE that precedes ESTRUS. During proestrus, the Graafian follicles undergo maturation.Norpregnadienes: Pregnadienes which have undergone ring contractions or are lacking carbon-18 or carbon-19.Pituitary Gland, Anterior: The anterior glandular lobe of the pituitary gland, also known as the adenohypophysis. It secretes the ADENOHYPOPHYSEAL HORMONES that regulate vital functions such as GROWTH; METABOLISM; and REPRODUCTION.Menstruation: The periodic shedding of the ENDOMETRIUM and associated menstrual bleeding in the MENSTRUAL CYCLE of humans and primates. Menstruation is due to the decline in circulating PROGESTERONE, and occurs at the late LUTEAL PHASE when LUTEOLYSIS of the CORPUS LUTEUM takes place.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)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.Phytoestrogens: PLANT EXTRACTS and compounds, primarily ISOFLAVONES, that mimic or modulate endogenous estrogens, usually by binding to ESTROGEN RECEPTORS.Gonadal Hormones: 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.Perimenopause: The transitional period before and after MENOPAUSE. Perimenopausal symptoms are associated with irregular MENSTRUAL CYCLE and widely fluctuated hormone levels. They may appear 6 years before menopause and subside 2 to 5 years after menopause.Dehydroepiandrosterone Sulfate: The circulating form of a major C19 steroid produced primarily by the ADRENAL CORTEX. DHEA sulfate serves as a precursor for TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE.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.Medroxyprogesterone Acetate: A synthetic progestin that is derived from 17-hydroxyprogesterone. It is a long-acting contraceptive that is effective both orally or by intramuscular injection and has also been used to treat breast and endometrial neoplasms.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.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Fertilization in Vitro: An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro.Anovulation: Suspension or cessation of OVULATION in animals or humans with follicle-containing ovaries (OVARIAN FOLLICLE). Depending on the etiology, OVULATION may be induced with appropriate therapy.Estrus Synchronization: Occurrence or induction of ESTRUS in all of the females in a group at the same time, applies only to non-primate mammals with ESTROUS CYCLE.Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Administration, Cutaneous: The application of suitable drug dosage forms to the skin for either local or systemic effects.Anabolic Agents: These compounds stimulate anabolism and inhibit catabolism. They stimulate the development of muscle mass, strength, and power.Leuprolide: A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE.Anestrus: A state of sexual inactivity in female animals exhibiting no ESTROUS CYCLE. Causes of anestrus include pregnancy, presence of offspring, season, stress, and pathology.Levonorgestrel: A synthetic progestational hormone with actions similar to those of PROGESTERONE and about twice as potent as its racemic or (+-)-isomer (NORGESTREL). It is used for contraception, control of menstrual disorders, and treatment of endometriosis.Hydroxyestrones: Estrone derivatives substituted with one or more hydroxyl groups in any position. They are important metabolites of estrone and other estrogens.Hypogonadism: Condition resulting from deficient gonadal functions, such as GAMETOGENESIS and the production of GONADAL STEROID HORMONES. It is characterized by delay in GROWTH, germ cell maturation, and development of secondary sex characteristics. Hypogonadism can be due to a deficiency of GONADOTROPINS (hypogonadotropic hypogonadism) or due to primary gonadal failure (hypergonadotropic hypogonadism).Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.Pregnancy, Animal: The process of bearing developing young (EMBRYOS or FETUSES) in utero in non-human mammals, beginning from FERTILIZATION to BIRTH.Phenols: Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.Vagina: The genital canal in the female, extending from the UTERUS to the VULVA. (Stedman, 25th ed)Hypothalamus, Middle: Middle portion of the hypothalamus containing the arcuate, dorsomedial, ventromedial nuclei, the TUBER CINEREUM and the PITUITARY GLAND.Gynecomastia: Enlargement of the BREAST in the males, caused by an excess of ESTROGENS. Physiological gynecomastia is normally observed in NEWBORNS; ADOLESCENT; and AGING males.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.Gonadotropins, Pituitary: Hormones secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR) that stimulate gonadal functions in both males and females. They include FOLLICLE STIMULATING HORMONE that stimulates germ cell maturation (OOGENESIS; SPERMATOGENESIS), and LUTEINIZING HORMONE that stimulates the production of sex steroids (ESTROGENS; PROGESTERONE; ANDROGENS).Follicular Atresia: The degeneration and resorption of an OVARIAN FOLLICLE before it reaches maturity and ruptures.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Rats, Long-Evans: An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Administration, Intravaginal: The insertion of drugs into the vagina to treat local infections, neoplasms, or to induce labor. The dosage forms may include medicated pessaries, irrigation fluids, and suppositories.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Enclomiphene: The trans or (E)-isomer of clomiphene.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Contraceptive Agents: Chemical substances that prevent or reduce the probability of CONCEPTION.Norethindrone: A synthetic progestational hormone with actions similar to those of PROGESTERONE but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception.Sex Differentiation: 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.Pituitary Hormone-Releasing Hormones: Peptides, natural or synthetic, that stimulate the release of PITUITARY HORMONES. They were first isolated from the extracts of the HYPOTHALAMUS; MEDIAN EMINENCE; PITUITARY STALK; and NEUROHYPOPHYSIS. In addition, some hypophysiotropic hormones control pituitary cell differentiation, cell proliferation, and hormone synthesis. Some can act on more than one pituitary hormone.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Pregnancy Rate: The ratio of the number of conceptions (CONCEPTION) including LIVE BIRTH; STILLBIRTH; and fetal losses, to the mean number of females of reproductive age in a population during a set time period.Reproduction: The total process by which organisms produce offspring. (Stedman, 25th ed)