Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycystic ovarian disease (PCO) is characterized by hyperandrogenism, ovulatory dysfunction, and altered gonadotropin secretion. Mean plasma FSH concentrations are low, while LH is elevated in a majority of patients. LH pulsatile secretion has been shown to occur at rapid follicular phase frequencies (approximately one pulse per h) in PCO, suggesting persistent rapid frequency GnRH secretion in this disorder. Anovulatory women with PCO were given estradiol (E2; Estraderm skin patches) and progesterone (P; vaginal suppositories) to produce midluteal concentrations for 21 days. The aim was to determine if E2 and P would slow LH (GnRH) pulse frequency and if this would result in augmented FSH secretion and follicular development after withdrawal of E2 and P. Plasma LH was measured every 10 min for 8 h before, during (days 10 and 20), and 7 days after withdrawal of E2 and P (day 28). On each of these study days FSH was measured hourly, and E2 and P were measured every 2 h. After sampling, GnRH (25 and 250 ng/kg, iv) was given to assess pituitary responsiveness. Follicular development was monitored by vaginal ultrasound through day 34 of the study. Basal LH frequency was 8.5 +/- 0.5 pulses/8 h (mean +/- SEM). During E2 and P, LH pulse frequency fell to 3.3 +/- 1.0 (10 days) and 2.3 +/- 0.8 (20 days), 39% and 27% of the basal value, respectively, and subsequently increased to 5.6 +/- 0.7 (66% of basal) 7 days after withdrawal of E2 and P. LH pulse amplitude (basal, 7.2 +/- 1.5 IU/L) was not reduced until day 20, but remained suppressed (3.9 +/- 1.1 IU/L) on day 28. As a result, mean LH (basal, 21.0 +/- 3.5 IU/L) fell progressively during E2 and P, to 3.8 +/- 1.2 IU/L on day 20, and remained low (39% of basal) 7 days after steroid withdrawal. Mean plasma FSH (basal, 7.1 +/- 0.9 IU/L) also fell during steroid administration, but in contrast to LH, had risen to 93% of the basal value by 7 days after E2 and P. LH release in response to exogenous GnRH revealed marked initial responses which did not decrease until day 20, but remained suppressed (8% of basal) after withdrawal of E2 and P. FSH responses were also suppressed on day 20, but had increased to 75% of the basal value by day 28. Initiation of follicular development occurred in all patients, and the lead follicle measured 12.3 +/- 0.8 mm 13 days post-E2 and P. Ovulation occurred in one patient.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reduction of gonadotropin-releasing hormone pulse frequency is associated with subsequent selective follicle-stimulating hormone secretion in women with polycystic ovarian disease. 190 45

We have previously reported that during 2 months of strenuous exercise, untrained young women with documented ovulatory menstrual cycles developed secondary oligoamenorrhea and luteal phase defects. In this study we tested the hypothesis that such abnormalities arise by altered neuroendocrine regulation of menstrual hormone secretion and that weight loss potentiates such effects. We supply a detailed analysis of the 20 cycles, of the total of 53, in which luteal phase abnormalities occurred. During the control month and 2 exercise months, all subjects collected daily overnight urine samples for the determination of LH, FSH, estriol (E3), and free progesterone (P) excretion by RIAs and creatinine by chemical assay. The characteristics of the abnormal luteal phase cycles were determined by comparing the excreted hormone levels and patterns during the control cycles with those of exercise cycles. The area under the curve (AUC) for each hormone was calculated for the follicular and luteal phases of each cycle. Six of the exercise cycles exhibited an inadequate luteal phase. This was characterized by a mean integrated P area of 202.4 (SEM, -61.8) nmol/day.nmol creatinine, compared with 331.7 (SEM, 64.7) during the corresponding control cycles, over a period of 9 or more days after the urinary LH peak to the onset of menses. Fourteen of the exercise cycles exhibited a short luteal phase. This was characterized by a mean integrated P area of 75.9 (30.9) nmol/day.nmol creatinine, compared to 267 (61.7) during the corresponding control cycles, over a span of 8 days or less from the urinary LH peak to the onset of menses. Additional abnormalities occurred only in the short luteal phase cycles. These included an increase in the length and AUC for E3 of the follicular phase and a decrease in the AUC of LH during the luteal phase. We conclude that the initiation of strenuous endurance training in previously ovulating untrained women frequently leads to corpus luteum dysfunction associated with insufficient P secretion and, in the case of short luteal phase cycles, decreased luteal phase length. That exercise may alter the neuroendocrine system is suggested by a delay in the ovulatory LH peak in spite of increased E3 excretion; moreover, less LH is excreted during the luteal phase. The lack of positive feedback to estrogens and decreased LH secretion during the luteal phase could compromise corpus luteum function. In contrast, decreased free P excretion was the sole abnormality noted in menstrual cycles with an inadequate luteal phase.
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PMID:Exercise induces two types of human luteal dysfunction: confirmation by urinary free progesterone. 190 47

Gonadal involvement in fetal FSH regulation was examined by studying FSH levels in 13 female (7 castrate and 6 sham control) and 13 male (8 castrate and 5 sham control) chronically catheterized ovine fetuses operated upon in utero at 106-115 days gestation (term = 147 days). These fetuses had been studied previously for pulsatile LH secretion every 2-7 days over a 2- to 38-day period until fetal delivery or death. From each study day, 3 1-h spaced blood samples (1.5-2.0 ml) were taken for FSH determination by RIA (NIH FSH-S8 standard), and the results were averaged. The overall mean was then calculated for each fetus. In female fetuses, there was no significant difference in mean serum FSH levels between castrates [53.4 +/- 5.0 ng/ml (+/- SEM)] and controls (52.5 +/- 14.4 ng/ml). In contrast, serum FSH levels in the eugonadal males were significantly (P less than 0.001) lower (23.4 +/- 8.0 ng/ml) than those in castrate males (56.9 +/- 7.1 ng/ml, a value comparable to those observed in both female groups). Mean serum FSH levels declined significantly (P less than 0.001) in castrate fetuses of both sexes after 125 days (61.5 +/- 5.6 vs. 42.4 +/- 7.7 ng/ml in females; 64.1 +/- 6.1 vs. 51.5 +/- 8.6 ng/ml in males). In the males, the FSH decline did not reach sham control levels, which remained unchanged with advancing gestation. Moreover, mean serum FSH levels were significantly higher in a group of 4 male fetuses (62.2 +/- 13.7 ng/ml) castrated at 121-130 days gestation compared to values in 3 age-matched sham castrate controls (22.1 +/- 2.6 ng/ml; P less than 0.001). The increment in serum FSH levels in castrate compared to sham castrate male fetuses demonstrates an important role for the fetal testis in FSH regulation from 106 days gestation until term. The lack of a detectable castration effect on the relatively high serum FSH levels in eugonadal females indicates that the fetal ovary does not play a similar role and suggests that in females, FSH is secreted in a functionally castrate mode. The decline in FSH levels after 125 days in castrate fetuses of both sexes may result at least in part from the previously reported coincident rise in circulating levels of feto-placental sex steroids and/or PRL.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Control of gonadotropin secretion in the ovine fetus. III. Effect of castration on serum follicle-stimulating hormone levels during the last trimester of gestation. 190 76

The amplitude and duration of the midcycle LH surge required for ovulatory maturation of the follicle and its enclosed oocyte in primates are unknown. To titrate periovulatory LH requirements, female rhesus monkeys received human gonadotropins (FSH with/without LH) for 9 days beginning at menses to promote the development of multiple preovulatory follicles. The next day, animals (n = 4-6/group) received: 1) no ovulatory stimulus; 2) 1000 IU hCG, im; 3) one injection of 100 micrograms GnRH, sc (GnRH-1); 4) three injections of GnRH (GnRH-3) at 3-h intervals (0800, 1100, and 1400 h); or 5) two injections of 50 micrograms GnRH agonist (GnRHa), sc, 8 h apart (0800 and 1700 h) to induce ovulatory maturation. Follicles were aspirated 27 h after the hCG or initial GnRH/GnRHa injection or on days 8 and 10 in animals receiving no ovulatory stimulus. Nuclear maturity of oocytes was evaluated as a marker for reinitiation of meiosis. Estradiol and progesterone levels were determined in daily serum samples by RIA. Levels of LH(-like) bioactivity were measured at selected intervals after hCG injection and within 24 h of GnRH/GnRHa treatment. In all groups, estradiol continuously rose to similar peak levels on day 10. The hCG treatment markedly elevated circulating LH-like bioactivity for up to 3 days. In GnRH-1, bioactive LH increased to 433.1 +/- 170.2 ng/mL (mean +/- SEM; n = 3) within 1-2 h, but then decreased to baseline (4.9 +/- 1.5 ng/mL) within 6 h. GnRH-3 and GnRHa treatment extended the interval of elevated bioactive LH to 8 and 14 h, respectively. There was no difference in the peak levels of LH(-like) bioactivity reached after hCG, GnRH, or GnRHa injection. Functional luteal phases were absent in monkeys receiving no ovulatory stimulus, whereas hCG treatment increased progesterone levels to 101 +/- 9 nmol/L (n = 6) and elicited functional luteal phases of 11.8 +/- 0.4 days. In contrast, only one animal in the GnRH/GnRHa groups (i.e. one GnRH-3 monkey) displayed elevated progesterone levels in the luteal phase. Of the total cohort of oocytes aspirated from follicles, a greater (P less than 0.05) proportion were classified as being in metaphase I or II of meiosis after hCG treatment (86%) compared to no ovulatory stimulus (13%), GnRH-1 (0%), GnRH-3 (43%), and GnRHa (12%). Thus, GnRH elicits a transient LH surge that can be extended by GnRH-3 or GnRHa in stimulated cycles of monkeys.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Titrating luteinizing hormone surge requirements for ovulatory changes in primate follicles. I. Oocyte maturation and corpus luteum function. 190 81

In the male rat, age-associated reproductive decline is thought to be due in part to diminished GnRH secretion. We tested the hypothesis that the age-related decrease in GnRH secretion is due to decreased GnRH gene expression by comparing GnRH mRNA and peptide content in the anterior forebrain of intact young and old male rats. Since sex steroids modulate GnRH secretion, we also determined hypothalamic-pituitary responsiveness to removal of testicular feedback by comparing GnRH mRNA and gonadotropin levels in intact and orchidectomized young and old rats. In an initial study, 10 20-micron coronal sections from the medial preoptic area (MPOA) were anatomically matched and compared in intact young (3-month-old) and old (24-month-old) male F344 rats (n = 5/group). In another group of young and old male rats (n = 8-12/group), animals were randomly assigned to be either orchidectomized or sham operated. Rats were killed 21 days after surgery, and comparisons were made in 12 anatomically matched sections of MPOA and 4 matched sections of diagonal band of Broca. In both studies, GnRH mRNA was quantitated by in situ hybridization, using a 35S-labeled oligodeoxynucleotide probe complementary to rat prepro-GnRH mRNA and a computerized image analysis system. In a third study, GnRH content was measured by RIA in microdissected regions of the arcuate nucleus and median eminence in intact 3- and 24-month-old male rats (n = 10 and 8, respectively). Serum LH, FSH, and testosterone (T) levels were measured by RIA in trunk blood of all animals. The number of neurons expressing the GnRH gene in the MPOA was significantly lower in sham-operated old rats (mean +/- SEM, 10.5 +/- 0.5 cells/section) than in young rats (13.7 +/- 0.7 cells/section; P less than 0.01), while cellular GnRH mRNA content was unchanged with age (103 +/- 1 vs. 103 +/- 2 grains/cell). Similar results were obtained in intact old and young rats. GnRH peptide content was significantly decreased in the arcuate nucleus of intact old (0.5 +/- 0.08 ng/mg protein) compared to young animals (2.3 +/- 0.7 ng/mg protein; P less than 0.05), with a trend toward a decrease in the median eminence of old (53 +/- 2 ng/mg protein) vs. young rats (69 +/- 7 ng/mg protein; P = 0.06).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Age-related decreases in serum gonadotropin levels and gonadotropin-releasing hormone gene expression in the medial preoptic area of the male rat are dependent upon testicular feedback. 193 78

The gonadotropin dependence of ovarian follicular maturation and corpus luteum function can now be examined in women using antagonistic analogs of GnRH. We studied the responses of three groups of women throughout a control cycle and during the administration of a potent GnRH antagonist, detirelix ([N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10++ +] GnRH, Syntex Research). Detirelix (10 mg, sc) was administered for 3 consecutive days during the midfollicular phase (n = 4), preovulatory phase (n = 4), and early luteal phase (n = 4). The pituitary response to detirelix was similar throughout the three phases of the menstrual cycle. Immunoreactive LH concentrations decreased to 35% (mean +/- SEM) of pretreatment values within 8 h after the initial injection and remained suppressed for 72 h after discontinuance of treatment. Immunoreactive FSH concentrations decreased to 73 +/- 3% of pretreatment levels within 8 h and returned to baseline within 24 h after the third injection. In contrast, the ovarian response to detirelix varied markedly during different phases of the cycle. Midfollicular phase treatment was associated with a decline in estradiol (E2) levels from pretreatment values of 246 +/- 48 to 81 +/- 15 pmol/L within 24 h of the last injection. Vaginal bleeding ensued in three of four women. Follicular recruitment was then reinitiated, and an ovulatory LH surge occurred 18.2 +/- 2.9 days after the last injection. Similarly, treatment during the early luteal phase produced a decline in E2 concentrations from 286 +/- 29 to 70 +/- 7 pmol/L and a decline in progesterone concentrations from 20 +/- 1.6 to 1.9 +/- 0.3 nmol/L within 24 h after the last injection. Luteolysis was associated with menstrual bleeding in all four women. The subsequent ovulatory LH surge occurred 16.5 +/- 1.0 days after discontinuance of treatment. In contrast, treatment during the preovulatory phase resulted in a decline in E2 concentrations from 844 +/- 66 to 429 +/- 132 pmol/L during the first 48 h of treatment. Gonadotropin and E2 concentrations subsequently recovered from suppression, growth of the dominant follicle resumed, and a LH surge occurred 5.8 +/- 1.4 days after the last injection. These data indicate that the GnRH antagonist detirelix produces rapid and consistent suppression of pituitary gonadotropin secretion. The magnitude of suppression and preferential suppression of LH vs. FSH are similar throughout the cycle. In contrast, the ovarian response to gonadotropin deprivation varies during the menstrual cycle.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Variable ovarian response to gonadotropin-releasing hormone antagonist-induced gonadotropin deprivation during different phases of the menstrual cycle. 200 18

The ability of a potent long-acting antagonistic analog of GnRH to suppress gonadotropin secretion, disrupt follicular development, and inhibit ovulation was studied in six women with normal menstrual cycles. The GnRH antagonist detirelix ([N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10++ +] GnRH; Syntex Research) was administered to six women by sc injection on alternate days during a 27-day period. Six additional women underwent blood sampling only, without receiving detirelix. Within 8 h after the initial injection of detirelix, mean (+/- SEM) serum LH and FSH concentrations decreased by 74 +/- 2% and 26 +/- 3%, respectively. Mean immunoreactive FSH levels, however, returned to baseline after the first 72 h despite continued administration of detirelix. Mean estradiol (E2) concentrations decreased from 165 +/- 15 to 70 +/- 11 pmol/L in the first 24 h. During the treatment period follicular development was inhibited, and none of the six volunteers showed evidence of ovulation, as assessed by serum progesterone (P) levels. Maximal suppression of serum LH and E2 was observed approximately 24 h after each injection of detirelix. Compared to the control volunteers, those receiving detirelix had significantly lower mean serum LH (P less than 0.001), E2 (P less than 0.001), and P (P less than 0.001) levels during treatment; mean FSH concentrations, however, were not statistically different in the treatment and control groups. Rapid recovery of pituitary-ovarian function occurred after completion of treatment. In all six volunteers receiving detirelix, a LH surge occurred 10-16 days after the final injection, followed by increased P levels (greater than 32 nmol/L), indicating ovulation and a luteal phase of normal duration (12-14 days). Detirelix injections elicited local skin reactions (erythema and pruritus), but no systemic side-effects were observed. Thus, this long-acting GnRH antagonist can rapidly suppress gonadotropin secretion, inhibit follicular development, and prevent ovulation.
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PMID:Inhibition of follicular development by a potent antagonistic analog of gonadotropin-releasing hormone (detirelix). 200 20

To determine influences of insulin and body condition on follicular growth, prepuberal gilts (n = 16) treated with pregnant mare's serum gonadotropin (PMSG) were used in a 2 X 2 factorial experiment with main effects of insulin (0 or .4 IU/kg every 12 h beginning at 1800 on the day before PMSG) and backfat depth (moderate, 25 +/- .8; high, 32 +/- .7 mm; P less than .0001). Body weights were similar. Blood sampling was at 6-h intervals for analyses of LH, FSH, growth hormone (GH), glucagon, cortisol, insulin, insulin-like growth factor-I (IGF-I), plasma urea nitrogen (PUN), nonesterified fatty acids (NEFA), testosterone, estradiol-17 beta, and progesterone. Ovaries were removed 75 h after PMSG treatment, and visible small (less than or equal to 3 mm), medium (4 to 6 mm), large (greater than or equal to 7 mm), and macroscopically atretic follicles were counted. Administration of insulin increased IGF-I in fluid of medium follicles (108.8 vs 60.7 ng/ml; SEM = 13.3; P less than .05). Neither insulin nor fatness affected hCG binding by granulosa cells (12.5 +/- 1.6 ng/10(6) cells) or numbers of large (16.7 +/- 2.6) and medium (10.4 +/- 2.3) follicles. However, insulin increased the number of small follicles (58.9 vs 29.9; SEM = 9.7; P less than .05) and reduced the number of atretic follicles (3.8 vs 11.3; SEM = 1.1; P less than .05). The predominant effect of insulin on reducing number of atretic follicles was in the small size class (.6 vs 6.9; SEM = .6, P less than .01). Follicular fluid estradiol and progesterone were not affected by treatments; however, testosterone concentrations in large follicles were lower in gilts with higher backfat (32.5 vs 59.9 ng/ml; SEM = 4.0; P less than .05). Systemic LH, FSH, glucagon, cortisol, PUN, NEFA, estradiol, and testosterone were not affected by insulin or level of feeding. However, GH was lower in gilts that had higher backfat (overall average of 3.2 vs 2.8 ng/ml; SEM = .1; P less than .05). Insulin reduced atresia and altered intrafollicular IGF-I independently of body condition and without sustained effects on other hormones.
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PMID:Effects of exogenous insulin and body condition on metabolic hormones and gonadotropin-induced follicular development in prepuberal gilts. 206 18

Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usually does not produce clinical manifestations. This report describes primary cortisol resistance in a boy with isosexual precocity. A 6 7/12-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) tests. There were no features of glucocorticoid excess. Serum androstenedione and dehydroepiandrosterone concentrations were 4.7 +/- 0.3 nmol/L (mean +/- SEM of four measurements; normal less than 1.2) and 13.5 nmol/L (single measurement; normal, 1.0-2.2), respectively. The serum testosterone concentration was 0.9 nmol/L (normal, less than 0.7), and FSH and LH were normal. Serum cortisol concentrations were 1590 +/- 110 nmol/L (normal, 190-630) and 580 +/- 60 nmol/L (normal, 50-410) at 0800 and 2000 h, respectively. Serum cortisol responded normally to insulin-induced hypoglycemia. Glucocorticoids and adrenal androgens were resistant to suppression by dexamethasone. The Kd of [3H]dexamethasone binding to the glucocorticoid receptors of mononuclear leukocytes was increased (6.4 +/- 0.8 nM; mean +/- SEM of four determinations; normal, 1.4-3.4; P less than 0.001), but the binding capacity was normal. This patient with isosexual precocity has PCR, as indicated by functionally abnormal glucocorticoid receptors and hypercortisolism without other clinical or biochemical manifestations of Cushing's syndrome. Excessive adrenal stimulation by ACTH caused increased secretion of both cortisol and adrenal androgens, and the latter caused the clinical manifestations. PCR should be considered in other male children with isosexual precocity or female children with heterosexual precocity.
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PMID:Primary cortisol resistance presenting as isosexual precocity. 210 34

In superovulated women the pituitary response to GnRH is markedly attenuated by an unspecified ovarian factor(s). To examine the site of attenuation, the response of the pituitary to GnRH was investigated in five normally ovulating women during the late follicular phase of 3 cycles, i.e. a spontaneous (control) cycle, a cycle treated with 'pure' FSH, and a cycle treated with a combination of 'pure' FSH and pulsatile GnRH, via a pump (15 micrograms/pulse). The oestradiol levels (mean +/- SEM) at the time of the GnRH challenge were respectively 646 +/- 35, 1692 +/- 282 and 5976 +/- 1129 pmol/l. The size of the leading follicle was similar in all groups. Serum LH levels during treatment with FSH decreased significantly, while during treatment with FSH plus GnRH they increased initially and then decreased progressively. The response of pituitary LH to GnRH was significantly attenuated during treatment with FSH and FSH plus GnRH, as compared to the spontaneous cycles, but was not abolished. The attenuation was significantly greater in the FSH plus GnRH cycles (94%) than in the FSH cycles (59%). We conclude that in superovulated cycles, the attenuation of the pituitary response to GnRH increases with the degree of ovarian hyperstimulation. It is suggested that the responsible unspecified ovarian factor(s) exerts its effects at least at the pituitary level.
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PMID:Superovulation induction in women suppresses luteinizing hormone secretion at the pituitary level. 211 44


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