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Query: UMLS:C0003128 (anovulation)
 1,718 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anovulation in women with polycystic ovary syndrome results from a disorder of FSH-mediated follicular maturation which may involve paracrine modulation of FSH action by intra-ovarian factors. Epidermal growth factor (EGF) is a potent inhibitor of FSH-stimulated oestradiol production in the rat and has also been shown to inhibit aromatase activity in human granulosa cells obtained after superovulation. The purpose of this study was to investigate the action of EGF on granulosa cell function in human ovaries which had not been previously exposed to treatment with exogenous gonadotrophins and to compare the responses in tissue obtained from normal and from polycystic ovaries. Granulosa cells were obtained from antral follicles less than 10 mm in diameter after dissection of unstimulated normal or polycystic ovaries (PCO). Cells were pooled, washed, plated and incubated for 48h in the presence of 10(-7) M testosterone and various doses of human FSH. FSH dose responses were obtained with or without the addition of purified EGF (50 pg/ml). Testosterone in the absence of FSH resulted in a fourfold (range 2-7.5) increase in oestradiol accumulation in the medium after incubation of granulosa cells from both normal and polycystic ovaries. This increase was reversed by addition of EGF. FSH treatment stimulated a dose-related increase in oestradiol regardless of the origin of the granulosa cells. The peak E2 response to FSH, obtained at a dose of 1-2.5 ng/ml was a 20-fold increase above testosterone alone (range 4-55) in cells from PCO compared to sixfold (2.5-13) in cells from normal ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of oestradiol production by epidermal growth factor in human granulosa cells of normal and polycystic ovaries. 212 97

The structure of inhibin is known; it consists of a heterodimer composed of one alpha and one beta subunit. The homodimer of beta A (beta A-beta A) and the heterodimer beta A-beta B, called activin A and B, respectively, stimulate the release and synthesis of FSH by gonadotrophs. Inhibin exerts effects at the hypophyseal, hypothalamic, and gonadal levels. Produced by granulosa cells in the female and by Sertoli cells in the male, inhibin synthesis is stimulated by FSH and reduced by hypophysectomy and progesterone. At present, there is no evidence for a signal from germinal cells to modify inhibin production. Inhibin secretion evolves in parallel with follicular maturation and aromatase activity, whereas luteinization arrests its production. Nevertheless, important differences in the regulation of inhibin secretion seem to exist from one species to another. Sperm inhibin levels can be correlated with spermatozoa number. Administration of inhibin to sheep induces either anovulation or an increase in the rate of ovulation depending on the scheme of treatment.
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PMID:Inhibin and related peptides: mechanisms of action and regulation of secretion. 249 58

The structure of inhibin is known: it consists in a heterodimer constituted by one alpha and one beta subunits. The homodimer of beta A or the heterodimer beta A or the heterodimer beta A-beta B called activin A and B stimulates the release and the synthesis of FSH by gonadotrophs. Inhibin displays actions at hypophyseal, hypothalamic and gonadal levels. Produced by granulosa cells in female and by Sertoli cells in male, inhibin synthesis is stimulated by FSH, and reduced by hypophysectomy and progesterone. At the present time, there is no evidence for a signal from germinal cells to modify inhibin production. Inhibin secretion evolves with follicular maturation as aromatase activity whereas luteinization arrests its production. Nevertheless it seems to exist large difference in the regulation of inhibin secretion from one species to the other. Sperm inhibin levels are correlated with spermatozoa number. Its administration to the sheep induce either an anovulation or an increase of ovulation rate according to the scheme of treatment.
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PMID:Inhibin and related peptides. Mechanisms of action and regulation of secretion. 305 35

Chemical structure of inhibins is known: there are molecules constituted by two subunits alpha and beta (A or B). Inhibin displays actions at hypophyseal, hypothalamic and gonadal levels. Produced by granulosa cells in female and by Sertoli cells in male, inhibin synthesis is stimulated by FSH, androgens and reduced by hypophysectomy and progesterone. At the present time, there is no evidence for a signal from germinal cells to modify inhibin production. Inhibin secretion parallels with follicular maturation as aromatase activity whereas luteinization arrests its production. Sperm inhibin levels are correlated with spermatozoa number. Its administration to the sheep induces either an anovulation or an increase of ovulation rate according to the scheme of treatment.
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PMID:[Inhibin]. 332 59

This article reviews current knowledge of the effect of obesity on ovulation and reproductive potential. Although only a minority of obese women are affected, it seems certain that there is a link between obesity and anovulation. This interrelationship is suggested by the apparent effectiveness of weight reduction in suppressing the hyperandrogenemia observed with obesity and restoring ovulation. The increased aromatase activity and hyperinsulinemia observed in obese women is believed to play a major role in causing the hyperandrogenemia, either by stimulating luteinizing hormone secretion or directly stimulating the ovary. In addition to ovarian hyperandrogenemia, pituitary hypothalamic dysfunction has been observed in response to obesity. Inadequate central serotonin stimulation, excessive dopamine stimulation, and insensitivity to endorphins may all be involved in the pituitary hypothalamic dysfunction, as well as resistance to weight reduction. Few data are available on the efficacy of weight loss in restoring ovulatory function in obese women; nonetheless, weight reduction should be regarded as a central component of any attempt to induce ovulation. In terms of fertility, even a short-term weight loss can be beneficial. Ileal jejunal bypass surgery to effect weight reduction appears to place a fetus at risk; thus, avoidance of pregnancy for at least 2 years after such surgery is advised.
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PMID:Obesity and its effect on reproductive function. 390 6

We hypothesize that the Stein-Leventhal syndrome (type 1 polycystic ovarian disease: SLS-PCOD-I) results from an aberrant puberty. Abnormal neural development in the brain decreases the hypophyseal set-point for negative and positive ovarian hormone feedback. This generates a condition whereby hypophyseal luteinizing hormone (LH) secretion is inappropriately elevated compared to hypophyseal follicle-stimulating hormone (FSH) secretion and is thus termed inappropriate gonadotropin secretion (IGS). The events which create an initial state of IGS are referred to as the "generator" stage. IGS is maintained by ovarian-derived hyperandrogenemia and increased peripheral aromatization of androgens yielding elevated free serum estrone (E1) and unbound estradiol (E2) levels. E1 suppresses release of hypophyseal FSH while E2 exerts positive feedback on LH pulsatile release by increasing pituitary sensitivity to gonadotropin-releasing hormone (GnRH). Diminished circulating FSH levels decrease granulosa cell aromatase activity sufficiently to cause suboptimal ovarian conversion of LH-induced thecal androgens into estrogens. Consequently, chronic local ovarian hyperandrogenemia with associated arrested follicle maturation results in chronic anovulation. Furthermore, an elevated circulating LH/FSH ratio stimulates early development and proliferation of immature follicles causing the appearance of polyfollicular ovaries. In this effector stage of PCOD-I, a vicious cycle is fashioned wherein IGS causes polyfollicular ovaries and increased ovarian androgen production which, in turn, promotes IGS. We suggest that the etiology of this disease involves an aberrant puberty that establishes a persistent faulty hypothalamic-hypophyseal-ovarian axis.
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PMID:Hypothesis: aberrant puberty and the Stein-Leventhal syndrome. 614 82

Overall, significantly more antral follicles greater than or equal to 1 mm diameter were present in Romney ewes during anoestrus than in the breeding season (anoestrus, 35 +/- 3 (mean +/- s.e.m.) follicles per ewe, 23 sheep; Day 9-10 of oestrous cycle, 24 +/- 1 follicles per ewe, 22 sheep; P less than 0.01), although the mean numbers of preovulatory-sized follicles (greater than or equal to 5 mm diam.) were similar (anoestrus, 1.3 +/- 0.2 per ewe; oestrous cycle, 1.0 +/- 0.1 per ewe). The ability of ovarian follicles to synthesize oestradiol did not differ between anoestrus and the breeding season as assessed from the levels of extant aromatase enzyme activity in granulosa cells and steroid concentrations in follicular fluid. Although the mean plasma concentration of LH did not differ between anoestrus and the luteal phase of the breeding season, the pattern of LH secretion differed markedly; on Day 9-10 of the oestrous cycle there were significantly more (P less than 0.001) high-amplitude LH peaks (i.e. greater than or equal to 1 ng/ml) in plasma and significantly fewer (P less than 0.001) low amplitude peaks (less than 1 ng/ml) than in anoestrous ewes. Moreover, the mean concentrations of FSH and prolactin were significantly lower during the luteal phase of the cycle than during anoestrus (FSH, P less than 0.05, prolactin, P less than 0.001). It is concluded that, in Romney ewes, the levels of antral follicular activity change throughout the year in synchrony with the circannual patterns of prolactin and day-length. Also, these data support the notion that anovulation during seasonal anoestrus is due to a reduced frequency of high-amplitude LH discharges from the pituitary gland.
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PMID:Changes in gonadotrophin secretion and ovarian antral follicular activity in seasonally breeding sheep throughout the year. 642 May 56

Two long and broad streams of medical literature, from the 1950's to date, have established the existence of two unrelated abnormalities of androgen production in women with breast cancer. One is the genetically determined presence of subnormal production of adrenal androgens (i.e. DHEA and DHEAS) in women with premenopausal breast cancer and their sisters, who are at increased risk for breast cancer. The other is excessive production of testosterone, of ovarian origin, in subsets of women with either premenopausal or postmenopausal breast cancer and women with atypical breast-duct hyperplasia, who are at increased risk for breast cancer; along with the hypertestosteronism, there is frequently chronic anovulation in the premenopausal patients. The combination of ovarian hypertestosteronism and chronic anovulation is characteristic of the polycystic ovary syndrome and is also frequently seen in women with abdominal ("android") obesity; both PCOS and abdominal obesity are known to be characterized by high risk for postmenopausal cancer. The elevated testosterone levels and the increased levels of insulin, IGF-I, and IGF-II that are seen in PCOS and abdominal obesity could favor the development of breast cancer in several ways, all of which have been demonstrated experimentally: binding of testosterone to cancer cells bearing testosterone receptors, with direct stimulation; intratissular aromatization of testosterone to estradiol, with stimulation of estrogen-sensitive cells; stimulation of the production of epithelial growth factor (EGF) by testosterone, with direct mitogenic effect of EGF on cancer cells; stimulation of aromatase by insulin and IGF-I; direct mitogenic stimulation of cancer cells by insulin, IGF-I, and IGF-II; and stimulation by IGF-I and IGF-II of the intratissular reduction of estrone to estradiol. Since PCOS is probably largely genetically determined, and abdominal obesity may also be, the hypertestosteronism of these conditions may represent a second genetically determined hormonal risk factor for breast cancer.
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PMID:Abnormal production of androgens in women with breast cancer. 784 May 9

The underlying cause of anovulation in polycystic ovary syndrome is unknown. Circulating levels of immuno- and bioactive FSH are within the normal range, and the follicles contain measurable levels of bioactive FSH. The aim of this study was to compare estradiol (E2) production in response to FSH by granulosa cells from normal ovaries with those from polycystic ovaries derived from both anovulatory (anovPCO) and ovulatory subjects (ovPCO). Intrafollicular levels of immunoactive FSH, E2, and androstenedione in follicles of less than 12 mm were also measured. Follicular fluid steroid concentrations were obtained from 41 pairs of normal ovaries and 23 pairs of polycystic ovaries (8 anovPCO and 15 ovPCO). In size-matched follicles from each group there were no significant differences in follicular fluid FSH or E2 concentrations, but androstenedione levels were significantly higher in 5- to 11-mm follicles from ovPCO than in corresponding follicles from normal ovaries. Dose responses to FSH were determined in granulosa cells derived from 9 pairs of normal ovaries, 7 anovPCO, and 8 ovPCO. Cells from anovPCO produced 6- to 10-fold more E2 in response to FSH than normal cells, although there was no significant difference in the ED50 values. The response in cells from ovPCO was reduced compared to normal, but this difference did not reach significance. In summary, as judged by their FSH and E2 contents, polycystic ovaries do not have a higher proportion of atretic follicles than normal. Indeed, cells from anovPCO are hyperesponsive to FSH in vitro. This could be explained by stimulation of aromatase in vivo by either paracrine or, more probably, by endocrine factors, of which insulin is an arguable candidate.
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PMID:Estradiol production by granulosa cells of normal and polycystic ovaries: relationship to menstrual cycle history and concentrations of gonadotropins and sex steroids in follicular fluid. 796 30

To study the interrelationships of steroids within the follicle, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C] testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery. The concentrations of tracer and/or nonisotopic dehydroepiandrosterone sulfate, androst-5-ene-3 beta,17 beta-diol sulfate, androst-5-ene-3 beta,17 beta-diol, dehydroepiandrosterone, androstenedione, T, dihydrotestosterone, estrone (E1), and estradiol (E2) were determined in arterial and venous blood and follicular fluid. The log-transformed product/precursor ratio of [3H]dihydrotestosterone/[3H]T in follicular fluid was negatively correlated with the log-transformed follicular concentrations of E1 (P = 0.01) and E2 (P = 0.02), suggesting a reciprocal relationship between 5 alpha-reductase and follicular E1 and E2. E2 and T were positively correlated in follicular fluid (r = 0.84; P = 0.0003), suggesting a stimulatory action of follicular T on aromatase. These findings along with extensive published data suggest that follicular T functions as a follicular regulator, enhancing follicular aromatase activity when adequate amounts of FSH are available. These conclusions have important implications with regard to mechanisms for selecting the dominant follicle and producing atresia in the remaining cohort of follicles, and they describe a final common path in the pathophysiology of anovulation.
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PMID:Testosterone, a follicular regulator: key to anovulation. 837 Jun 94


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