Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003128 (anovulation)
 1,718 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

For 21 postpartum dairy cows studied during the period of negative energy balance, the rate of muscle protein degradation, gluconeogenic changes, circulating large neutral AA, and plasma IGF-I were measured to investigate their possible association with the duration of anovulation and LH secretions. Cows that ovulated (n = 17) were energetically deficient at first ovulation but were approaching a balanced state. The dynamic changes in energy balance, but not the mean energy balance or the extent of BW loss, were correlated with days to first ovulation. Variations in energy balance were explained largely by variations in energy intake. Increased mobilization of body protein was indicated by higher concentrations of 3-methylhistidine during the first 3 wk postpartum and was not correlated with duration of postpartum anovulation. Plasma aspartate transaminase decreased significantly, and the proportion of Tyr to total large neutral AA significantly increased in the 12 d prior to first ovulation; both were correlated with LH secretion. Plasma IGF-I did not correlate with days to first ovulation, but correlated with LH pulse frequency. These findings indicate that decreased gluconeogenesis from AA is associated with duration of recovery and that Tyr may participate in metabolic signaling to the hypothalamus-hypophyseal axis controlling ovarian function in the postpartum dairy cow.
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PMID:Metabolic status and interval to first ovulation in postpartum dairy cows. 855 Sep

IGFs function as co-gonadotropins in the ovary, facilitating steroidogenesis and follicle growth. IGFBP-1 to -5 are expressed in human ovary and mostly inhibit IGF action in in vitro ovarian cell culture systems. In the clinical disorder of polycystic ovarian syndrome (PCOS), which is characterized by hyperandrogenemia, polycystic ovaries and anovulation, follicles have a higher androgen: estradiol (A : E2) content and growth is arrested at the small antral stage. In the PCOS follicle, follicle stimulating hormone (FSH) and IGF levels are in the physiologic range, and even in the face of abundant androstenedione (AD) substrate, aromatase activity and E2 production are low. When PCOS granulosa are removed from their ovarian environment, they respond normally or hyperrespond to FSH. It has been postulated that an inhibitor of IGF's synergistic actions with FSH on aromatase activity may be one (or more) of the IGFBPs, which contributes to the arrested state of follicular development commonly observed in this disorder. High levels of IGFBP-2 and IGFBP-4 are present in follicular fluid (FF) from androgen-dominant follicles (FFa) from normally cycling women and in women with PCOS. This is in marked contrast to the near absence of these IGFBPs in estrogen-dominant FF (FFe), determined by Western ligand blotting. Regulation of granulosa-derived IGFBPs is effected by gonadotropins and insulin-like peptides. In addition, an IGFBP-4 metallo-serine protease is present in FFe, but not in FFa in ovaries from normally cycling women and those with PCOS, although the IGFBP-4 protease is present in PCOS follicles hyperstimulated for in vitro fertilization. Recent studies demonstrate that IGF-II in FFe is higher than in FFa' whereas IGF-I, IGFBP-3 and IGFBP-1 levels do not differ, underscoring the importance of local IGF-II production by the granulosa and the importance of IGFBP-4 and IGFBP-2 in regulation of IGF-II action within the follicle during its developmental pathway as an E2- or A-dominant follicle. In the androgen-treated female-to-male transsexual (TSX) model for PCOS, IGF-I, IGF-II, IGFBP-3 and IGFBP-1 levels do not differ.
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PMID:Circulating and ovarian IGF binding proteins: potential roles in normo-ovulatory cycles and in polycystic ovarian syndrome. 881 83

The objectives of this study were to characterize early postpartum (PP) follicular development in dairy cows and to evaluate the influence of energy balance (EB) and the level of dietary fat on dominant follicle development and function. Forty-five multiparous Holstein cows were fed either low (LF, 3.3%), moderate (MF, 5.2%), or high (HF, 7.1%) total dietary fat beginning at parturition, and daily EB was determined for all cows. Follicular development was monitored by ultrasonography, and blood plasma was analyzed for metabolites, metabolic hormones, progesterone, estradiol, and FSH. After an increase (p < 0.01) in mean plasma FSH during Days 1-5, all cows experienced a wave of follicular development during the second week PP regardless of diet or EB. Feeding the MF (p < 0.05) or HF (p < 0.06) diet resulted in a greater number of class IV (> 15 mm) follicles on Day 14 PP as compared to the LF diet. Cows fed the MF diet had higher (p < 0.05) peak plasma estradiol during the first follicular wave and a shorter (p < 0.05) interval to first ovulation than both LF and HF cows. Follicular development prior to first ovulation was characterized by either ovulation of the first dominant follicle (OV, n = 19), one or more waves of nonovulatory dominant follicles (NOV, n = 18), or the formation of a follicular cyst (CYST, n = 8). Ovulation failure during the first follicular wave PP was accompanied by lower (p < 0.001) peak plasma estradiol (0.96 +/- 0.36 vs. 5.0 +/- 0.35 pg/ml), a smaller (p < 0.01) maximum follicle diameter (16.0 +/- 0.9 vs. 20.0 +/- 1.0 mm), lower (p < 0.09) levels of plasma insulin-like growth factor-I (IGF-I; 73.5 +/- 10.1 vs. 102.9 +/- 9.9 ng/ml), and a longer (p < 0.02) interval to the EB nadir (14.6 +/- 1.9 vs. 6.4 +/- 1.9 days). The number of days to first ovulation was positively correlated with days to the EB nadir (r = 0.55), with dominant follicles that emerged after the EB nadir exhibiting enhanced (p < 0.01) production of estradiol and greater (p < 0.01) ovulatory success. The development of large (> 10 mm) dominant follicles was not a limiting factor in PP reproductive recovery, and moderate dietary fat shortened the interval to first ovulation. Follicular competence early PP was associated with higher plasma IGF-I and a shorter interval to the EB nadir.
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PMID:Energy balance and ovarian follicle development prior to the first ovulation postpartum in dairy cows receiving three levels of dietary fat. 900 42

The objectives of this study were to relate energy balance and metabolic hormones during the early postpartum period in dairy cows with dominant follicle development before first ovulation and to evaluate the effects of prilled lipid on follicular development during the first follicular wave after parturition and the postpartum anovulatory interval. At parturition, 42 cows received a control diet (4.8% fat) or a diet supplemented with prilled fatty acids (7.0% fat). Energy balance was determined daily. Ovarian follicular development was monitored by ultrasonography, and blood plasma or serum was analyzed for estradiol, progesterone, and metabolic hormones. Dry matter intake was lower in cows supplemented with dietary lipids during the first 4 wk of lactation, but energy intake, energy balance, and the postpartum anovulatory interval were similar between diets. A wave of follicular development occurred in all cows during the 2nd wk postpartum, and 50% of all cows ovulated their first dominant follicle. Numbers of follicles that were 3 to 5 mm, 6 to 9 mm, and 10 to 15 mm on d 8 postpartum were similar between diets and unrelated to energy balance or metabolic hormones. Diameter of the dominant follicle during d 8 to 14 postpartum and maximum diameter of the first-wave ovulatory follicle did not differ between diets. Cows with nonovulatory first-wave dominant follicles had lower mean plasma concentrations of estradiol during d 8 to 14 postpartum, a longer interval to the day of the energy balance nadir, lower serum concentrations of IGF-I, and higher 4% FCM yield than did cows with ovulatory first-wave dominant follicles. Serum IGF-I during d 1 to 13 was positively correlated with plasma estradiol during d 8 to 14 postpartum. Possibly because of reductions in dry matter intake, the consumption of prilled lipid by dairy cows during early lactation may be ineffective in altering energy balance, follicular development, and the postpartum anovulatory interval. Ovulation failure of dominant follicles early in the postpartum period is associated with greater production of 4% fat-corrected milk, a delayed energy balance nadir, and reduced concentrations of peripheral IGF-I.
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PMID:Energy balance, metabolic hormones, and early postpartum follicular development in dairy cows fed prilled lipid. 949 87

Angus x Hereford heifers were used to determine endocrine and ovarian function preceding nutritionally induced anovulation. Six heifers were fed to maintain body condition score (M), and 12 heifers were fed a restricted diet (R) until they became anovulatory. Starting on d 13 of an estrous cycle, heifers were given PGF2alpha every 16 d thereafter to synchronize and maintain 16 d estrous cycles. Ovarian structures of M and R heifers were monitored by ultrasonography daily from d 8 to ovulation (d 1 of the subsequent cycle) until R heifers became anovulatory. Concentrations of LH and FSH were quantified in serum samples collected every 10 min for 8 h on d 2 and 15 (48 h after PGF2alpha), and estradiol and IGF-I were quantified in daily plasma samples from d 8 to 16 during the last ovulatory cycle (Cycle -2) and the subsequent anovulatory cycle (Cycle -1). During the last two cycles before anovulation, M heifers had 50% larger (P < .0001) ovulatory follicles than R heifers and 61% greater (P < .0001) growth rate of the ovulatory follicles. There was a treatment x cycle x day effect (P < .001) for concentrations of estradiol. The preovulatory increase in estradiol occurred in the R and M heifers during Cycle -2 but only in M heifers during Cycle -1. A treatment x cycle x day effect (P < .05) influenced LH concentrations. During Cycle -2, LH concentrations were similar for M and R heifers, but during Cycle -1, M heifers had greater LH concentrations than did R heifers. Concentrations of FSH were greater (P < .05) in R than M heifers after induced luteolysis when R heifers failed to ovulate. There was a treatment x cycle interaction (P < .05) for IGF-I concentrations, and M heifers had 4.7- and 8.6-fold greater IGF-I concentrations than did R heifers during Cycle -2 and -1, respectively. We conclude that growth rate and diameter of the ovulatory follicle, and concentrations of LH, estradiol, and IGF-I are reduced before the onset of nutritionally induced anovulation in beef heifers.
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PMID:Nutritionally induced anovulation in beef heifers: ovarian and endocrine function preceding cessation of ovulation. 1037 31

Polycystic ovary syndrome (PCOS) is the most common cause of anovulation in women. Previous studies suggest that the pathogenesis of PCOS may involve interrelated abnormalities of the insulin-like growth factor (IGF) and ovarian steroidogenesis systems. We investigated this hypothesis in fasting serum samples from 140 women with PCOS (age, 27.4 +/- 0.4 yr; body mass index, 26.3 +/- 0.5 kg/m2; mean +/- SEM). IGF-related parameters were also studied in a group of normoovulatory women (n = 26; age, 26 +/- 4 yr; body mass index, 23.6 +/- 4.3 kg/m2). For the PCOS group, the mean testosterone (T) level was 2.5 +/- 0.1 nmol/L, and it was significantly correlated with LH (r = 0.41; P < 10(-6)), estrone (r = 0.33; P = 0.016), estradiol (r = 0.18; P = 0.04), and androstenedione (AD; P < 10(-6)), but not with dehydroepiandrosterone sulfate (P = 0.71), a marker of adrenal steroidogenesis. T and AD were also related to total ovarian follicle number and ovarian size, as previously found with normoovulatory women (1). There were no differences between the PCOS subjects and the normoovulatory group for total IGF-I, IGF-II, or IGF-binding protein-3 (IGFBP-3). However, IGFBP-1 levels were significantly decreased in the PCOS group (1.0 +/- 0.2 vs. 7.3 +/- 1.1 ng/mL; P < 0.001) and were inversely correlated with serum insulin levels (r = -0.50; P < 10(-8)). Serum levels of free IGF-I (fIGF-I) were elevated (5.9 +/- 0.3 vs. 2.7 +/- 0.3 ng/mL; P < 0.001) in inverse relation with IGFBP-1 (r = -0.31; P = 0.046). Serum fIGF-I levels were related to total follicle number (r = - 0.35; P < 10(-4)) and to the ratio of sex hormone-binding globulin to T (r = -0.23; P = 0.009). However, these relationships were not independent of other variables. Despite the more than 2-fold elevation in fIGF-I levels, significant relationships between fIGF-I and markers of ovarian steroidogenesis (T, AD, estradiol, and estrone) could not be demonstrated. In conclusion, although we confirmed correlations between LH and hyperandrogenemia and have found abnormalities in the IGF system in a large cohort of PCOS subjects, a direct relationship between hyperandrogenism and the IGF system could not be shown. Previous studies suggest that elevated LH and hyperinsulinemia lead to excess ovarian androgen synthesis in PCOS and that the intraovarian IGF system is important for normal follicle development and may be important in the arrested state of follicle development in PCOS. However, the data presented in this cross-sectional study suggest that insulin-related changes in circulating IGFBP-1 and subsequent elevation of fIGF-I reflect insulin resistance and have little enhancing effects on ovarian steroidogenesis in this disorder.
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PMID:Elevated serum levels of free insulin-like growth factor I in polycystic ovary syndrome. 1048 60

Obesity is associated with considerably reduced plasma GH concentrations, which may contribute to anovulation in (obese) women with polycystic ovary disease (PCOS). This clinical investigation was undertaken to establish whether the GH release process is deranged in obese women with PCOS and, if so, whether the observed anomalies are features of the syndrome or a sequel of body fat accretion. To this end we sampled 24-h plasma GH concentration profiles at 10-min intervals in 15 obese PCOS patients [mean age, 29 yr (range, 20-38); percent body fat, 47 +/- 5.2%], 15 equally obese controls with regular menstrual cycles [age, 34 yr (range, 20-44); percent body fat, 48 +/- 4.9%], and 15 healthy age-matched lean controls [age, 34 yr (range, 21-45); percent body fat, 29 +/- 9.0%]. Compared with lean controls, obese PCOS patients exhibited a greater than 60% reduction in basal and a greater than 75% reduction in pulsatile and total daily GH secretion due to a 2.7-fold attenuation of burst mass and a lesser (1.4-fold) slowing of GH pulse frequency. The mean +/- SEM number of statistically significant GH peaks was 13.9 +/- 1.2/24 h, the endogenous GH half-life was 14.1 +/- 0.4 min, basal GH secretion was 5.0 +/- 0.7 mU/liter.24 h, and total secretion was 61.4 +/- 9.6 mU/liter.24 h in obese women with PCOS. None of these parameters differed from those in the body mass index-matched controls. The approximate entropy ratio was significantly increased in obese women (both PCOS and controls), indicating greater irregularity of the GH release process. Total GH secretion in patients and the two control groups correlated strongly and negatively with percent body fat (r = -0.775; P < 10(-8)). Serum concentrations of IGF-I and IGF-binding protein-3 were higher in patients with PCOS than in obese controls (P = 0.03 and P = 0.02, respectively), but the IGF-1/IGF-binding protein-3 ratio was equivalent in all three study groups. In conclusion, the profoundly reduced and irregular GH release in obese women with PCOS appears to be a corollary of body fat accretion and not of the syndrome per se.
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PMID:Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome. 1221 75

The effect of pulsatile infusion of gonadotropin-releasing hormone (GnRH) on follicular function was evaluated in nutritionally induced anovulatory beef cows. After 4 (short; n = 12) or 18 wk (long; n = 12) of anovulation, cows were randomly assigned within anovulatory group to either 2 microg of GnRH treatment or saline (control; i.v.) every hour for 5 d. Ovarian structures were monitored by daily ultrasonography. Growth rate of the largest follicle (P < 0.01) and maximal size of the largest follicle during treatment were greater (P < 0.01) for GnRH vs control cows. At exsanguination after 5 d of GnRH treatment, the size of the second-largest follicle was greater (P < 0.05) in short (i.e., 4 wk) anovulatory cows than in long (i.e., 18 wk) anovulatory cows and the largest follicle tended (P < 0.10) to be larger in long vs short anovulatory cows. Short anovulatory GnRH-treated cows had more small follicles than short anovulatory control cows or long anovulatory GnRH-treated or control cows (anovulation x GnRH; P < 0.10). Follicular fluid (FFL) concentrations of estradiol (P < 0.01) and androstenedione (P < 0.05) were greater in GnRH vs control cows. Concentrations of insulin-like growth factor-I were greater (P < 0.10) in large vs small follicles in cows that were anovulatory for 4 wk, but not in cows that were anovulatory for 18 wk. The amount of insulin-like growth factor-binding protein (IGFBP)-3 in FFL was greater (P < 0.05) in 4- vs 18-wk anovulatory cows. Amounts of IGFBP-2, -4, and -5 were greater (P < 0.001) in FFL of small (< 5 mm) vs large (> or = 5 mm) follicles regardless of treatment. We conclude that pulsatile treatment with GnRH for 5 d stimulates similar growth of the largest follicles in short- and long-term anovulatory beef cows, and that the duration of anovulation is not a major factor that limits follicular growth w hen anovulatory cowsare treated with GnRH. The primary intrafollicular factors associated with increased follicular size were increased concentrations of estradiol, progesterone, and insulin-like growth factor-I,and decreased concentrations of IGFBP-2, -4, and -5. Increased duration of anovulation was associated with decreased concentrations of IGF-I and IGFBP-3 in FFL.
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PMID:Influence of exogenous gonadotropin-releasing hormone on ovarian function in beef cows after short- and long-term nutritionally induced anovulation. 1254 68

Recent studies suggest that IGF-I is a crucial regulatory factor in follicular growth during early post-partum period. The aim of the present study was to determine in detail the changing profiles of metabolic and reproductive hormones in relation to ovulation of the dominant follicle (DF) of the first follicular wave post-partum in high-producing dairy cows. Plasma concentrations of related hormones in 22 multiparous Holstein cows were measured from 4 weeks pre-partum to 3 weeks post-partum, and the development of DF was observed with colour Doppler ultrasound. Thirteen cows showed ovulation by 15.2 days post-partum. Anovulatory cows showed higher GH and lower IGF-I levels than those in ovulatory cows during the peri-partum period. Each DF developed similarly, and a clear blood flow in the follicle wall was observed despite ovulation or anovulation. In addition, detailed endocrine profiles were analyzed in 9 out of the 22 cows. Five cows showed an increase in plasma oestradiol-17beta (E2) with follicular growth followed by E2 peak, LH surge and ovulation. In these cows, plasma IGF-I concentrations remained high until 10 days post-partum followed by a gradual decrease. Subsequently, the insulin level increased together with the E2 peak towards ovulation. These profiles were not observed in anovulatory cows. In conclusion, our data strongly support the concept that IGF-I and insulin represent 'metabolic signals' of the resumption of ovarian function post-partum in high-producing dairy cows. Moreover, we provide the first visual evidence that both ovulatory and anovulatory DFs of the first follicular wave post-partum are similarly supplied with active blood flow.
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PMID:Relationship between metabolic hormones and ovulation of dominant follicle during the first follicular wave post-partum in high-producing dairy cows. 1724 42


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