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)

Inhibin is a gonadal glycoprotein believed to be important in the regulation of pituitary FSH secretion and/or to function as a paracrine factor within the ovary and testis. We studied serum levels of inhibin, oestradiol (E2), progesterone (P), FSH and LH during the periovulatory interval in order to determine whether there is differential control of sex steroid and inhibin secretion by the mature follicle and the emerging corpus luteum. Seven normal cyclic women were admitted 3-4 days prior to midcycle and blood samples drawn every 3 h for 5-7 days. Serum E2, P, FSH, LH and inhibin were measured by radioimmunoassay. Data were normalized around the peak LH value (0 h). Serum E2 and inhibin rose in parallel (r = 0.92, P less than 0.001) between -69 and -18 h, E2 reached a peak of 1296 +/- 154 (mean +/- SEM) pmol/l at -18 h, then fell to 1050 +/- 139 pmol/l at 0 h. Serum inhibin, on the other hand, continued to rise to a peak of 837 +/- 95 U/l at -6 h, fell to 455 +/- 48 U/l at +45 h, then rose again. On average, the peak inhibin level occurred 10.4 +/- 5.1 h after the peak E2 (P less than 0.05). Inhibin levels were positively correlated with both serum LH and FSH between -24 and +24 h (P less than 0.01). Serum E2 was negatively correlated with LH, FSH and inhibin between -24 and 0 h (P less than 0.01). Serum P levels increased from 1.8 +/- 0.3 nmol/l at -24 h to 14.3 +/- 1.0 nmol/l at +60 h. Serum inhibin was positively correlated with serum P from -24 to 0 h (P less than 0.01) and +45 to +60 h (P less than 0.01), but was inversely correlated from 0 to +45 h (P less than 0.01). We conclude that the maturing follicle secretes both E2 and inhibin in parallel until -18 h, at which time the process of luteinization is initiated by the onset of the midcycle LH surge, as evidenced by the rise in P. E2 secretion then falls while inhibin secretion rises, indicating different regulation of secretion of these two hormones by the maturing follicle. Furthermore, the close positive correlation between inhibin and gonadotrophin levels around midcycle suggests that FSH and/or LH stimulate inhibin secretion and that the presumed negative feedback effect of inhibin on FSH secretion is overcome at this time. After midcycle, inhibin secretion initially falls, then rises, while P rises progressively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Serum inhibin levels during the periovulatory interval in normal women: relationships with sex steroid and gonadotrophin levels. 211 47

An experiment was conducted in order to determine the pattern of, and the relationships between, the secretion of inhibin, estradiol, and androstenedione by the ovary and the concentration of LH, FSH, and PRL during the estrous cycle of sheep. The estrous cycles of 6 Finn-Merino ewes in which the left ovary had been autotransplanted to the neck were synchronized by two injections of cloprostenol (100 micrograms im) a potent analog of prostaglandin F2 alpha (PG) given 14 days apart. The ewes had ovarian and jugular venous blood samples taken at four hourly intervals from 42 h before the second PG injection until day 6 of the following cycle. All animals responded to PG with the preovulatory LH surge occurring within 58 +/- 2 h (mean +/- SEM). The concentration of FSH in jugular venous plasma fell (P less than 0.001) after the induction of luteolysis and then exhibited 3 peaks, the first coincident with the LH surge, the second on day 1, and the third on day 6. After injection of PG the secretion rates of inhibin, estradiol, and androstenedione increased (P less than 0.05) within 4-8 h. After this increase in the early follicular phase the secretion rate of estradiol continued to rise until the time of the LH surge (P less than 0.001). Although the secretion of androstenedione and inhibin increased in the 36 h before the LH surge the magnitude of this rise was less marked than for estradiol and was not statistically significant. Within 4-8 h of the start of the LH surge the secretion of estradiol and androstenedione declined rapidly reaching barely detectable levels within 16 h (P less than 0.001). In contrast the secretion of inhibin increased after the LH surge reaching a broad peak (P less than 0.05) of approximately 16-h duration, coincident with the second peak of FSH. From days 2-6 mean secretion of inhibin remained relatively stable at 2-6 ng/min although considerable variation was observed in individual profiles. The rate of estradiol secretion increased steadily from its nadir on day 1 to a broad peak centered around day 3 (3-6 ng/min, P less than 0.001) followed by a decline until by day 6 the estradiol secretion rate was less than 1 ng/min (P less than 0.01). The secretory profile for PRL showed a close relationship with estradiol secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pattern of ovarian inhibin, estradiol, and androstenedione secretion during the estrous cycle of the ewe. 211 67

As a preliminary step in searching for a pharmacological treatment for gonadotroph adenomas, we administered the GnRH antagonist analog Nal-Glu GnRH to five patients, four men and a woman, with FSH-secreting gonadotroph adenomas in order to determine its effect on FSH secretion. Administration of a single 10-mg dose of Nal-Glu GnRH to four of the patients produced a significant decrease in the serum FSH concentration in two patients and returned the FSH level to normal in only one. Administration of 5 mg Nal-Glu every 12 h for 7 days, however, produced a significant (P less than 0.001) decrease, and to within the normal range, in four of the five patients (mean +/- SEM, 32.7 +/- 5.6 IU/L during the 3 days before treatment and 9.8 +/- 1.4 IU/L during the last 3 days of treatment). Also, in response to the 7-day treatment, LH fell significantly in all five patients, alpha-subunit fell in three, and testosterone fell in all four men. Administration for 6 weeks of the GnRH agonist analog leuprolide did not decrease the serum FSH concentration of one of the patients whose serum FSH did decrease in response to Nal-Glu GnRH. We conclude that repetitive administration of Nal-Glu GnRH may often inhibit FSH secretion by gonadotroph adenomas and that FSH secretion by gonadotroph adenomas may be dependent on endogenous GnRH secretion.
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PMID:Inhibition of follicle-stimulating hormone secretion from gonadotroph adenomas by repetitive administration of a gonadotropin-releasing hormone antagonist. 211 48

Gonadotroph adenomas may exhibit qualitative and quantitative defects in gonadotropin biosynthesis and secretion. Hypersecretion of immunoreactive FSH dimers by these adenomas occurs frequently; however, it has not been known whether this FSH is biologically active. Using the granulosa cell aromatase bioassay and a highly specific immunoradiometric assay for FSH, we studied the serum bioactivity and bio- to immunoactivity (B/I) ratios of 14 men with FSH-secreting adenomas and compared these values to those of 11 age-matched normal men. In addition, three adenoma patients received TRH (400 micrograms, iv). The mean basal serum FSH level (international units per L), as measured by both bio- and immunoassays, and the FSH B/I ratios were significantly higher (P less than 0.02, by Kolmogorov-Smirnov test) in the adenoma patients than in normal men (mean +/- SEM; adenoma patients: bioactivity, 68.8 +/- 10.4; immunoreactivity, 34.8 +/- 13.7; B/I ratio, 3.4 +/- 0.6; normal men: bioactivity, 5.8 +/- 1.2; immunoreactivity, 6.4 +/- 0.8; B/I ratio, 0.90 +/- 0.1). Both bio- and immunoactive FSH rose after TRH injection, resulting in maintenance of the B/I (mean +/- SEM; pre-TRH: bio-FSH, 63.7 +/- 22.4; immuno-FSH, 28.0 +/- 14.1; B/I ratio, 2.8 +/- 1.2; post-TRH: bio-FSH, 125.6 +/- 42.7; immuno-FSH, 45.8 +/- 21.8; B/I ratio, 3.5 +/- 1.6). When gonadotroph adenoma cells from three separate patients were cultured and their conditioned media (n = 3) studied, relatively large amounts of both bio- and immuno-FSH were detected. Furthermore, the major isoelectric profile of bio-FSH (pH 4.9-3.0) in the conditioned medium from two such adenomas was shown by chromatofocusing to be comparable to that of purified human pituitary FSH (pH 5.2-3.6). We conclude that gonadotroph adenomas in men secrete FSH that is biologically active, both basally and in response to TRH.
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PMID:Gonadotroph adenomas in men produce biologically active follicle-stimulating hormone. 211 91

To examine the relationship between circulating levels of bioactive FSH (B-FSH) and immunoactive inhibin and oestradiol we studied five women during ovulatory cycles. Daily blood samples were collected from each subject during one menstrual cycle. B-FSH was measured using a modified, highly sensitive in-vitro rat granulosa cell bioassay. The inclusion of IGF-1 (10 micrograms/l) and transferrin (50 mg/l) in the assay system enhanced granulosa cell responsiveness to FSH and resulted in increased assay sensitivity. Inhibin was measured by a heterologous radioimmunoassay (RIA) using an antibody raised against 31 kDa bovine inhibin. Bioactive FSH (B-FSH) levels were closely correlated to those of immunoactive FSH (I-FSH, r = 0.79, P less than 0.001) throughout the cycle. Peak levels of B-FSH were observed during the early follicular phase (day -13, 44.7 +/- 9.6 IU/l, mean +/- SEM) and during the midcycle surge (35.2 +/- 6.2 IU/l); lowest levels occurring during the luteal phase (nadir 3.9 +/- 0.27 IU/l). Plasma oestradiol levels increased significantly during the follicular phase (P less than 0.001) to a peak on day -1 and were negatively correlated with B-FSH during the late follicular phase (day -8 to -1; r = -0.45, P less than 0.02). There was no change in the concentration of inhibin (range 55.3-72.3 U/l) during the follicular phase until day -2 after which an increase to a midcycle peak of 139 +/- 10.6 U/l was observed. No correlation was observed between inhibin and B-FSH during the follicular phase. A second increase in the concentration of inhibin was seen during the luteal phase; peak levels occurred by day 6 (311 +/- 25.8 U/l), remained elevated until day 12, and were negatively correlated with B-FSH (r = -0.53, P less than 0.001). No correlation was observed between oestradiol and inhibin or B-FSH during the luteal phase. We conclude that (1) oestradiol secretion from the growing follicle is primarily responsible for the negative feedback regulation of B-FSH resulting in a change from peak levels in the early follicular phase to basal levels in the late follicular phase; (2) significant and sustained increase in peripheral inhibin concentrations occur mostly during the luteal phase; and (3) regulation of FSH secretion by inhibin occurs primarily in the luteal phase. These results suggest a temporal relationship between oestradiol and inhibin in the negative feedback regulation of FSH in vivo.
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PMID:Circulating bioactive follicle stimulating hormone and immunoreactive inhibin levels during the normal human menstrual cycle. 212 99

Serum bioactive and immunoreactive LH and FSH were measured in clinical conditions with increased or decreased gonadotropin secretion. Gonadotropin immunoreactivity was measured using a conventional RIA (I) and an ultrasensitive immunofluorometric method (F). Bioactive (B) LH was assessed by the mouse interstitial cells in vitro bioassay, and B-FSH using the immature rat granulosa cell assay. Acute GnRH stimulation of adult men (n = 6) increased LH levels measured by the different methods 4.3- to 5.3-fold. The B/I ratio of LH increased from 2.34 +/- 0.21 to 3.71 +/- 0.36 (mean +/- SEM) at 120 min (P less than 0.05), but no change was found in the B/F ratio. After ovariectomy of premenopausal women (n = 6), the LH levels increased in 1 week 4- to 6-fold, the B/I ratio from 1.85 +/- 0.22 to 2.59 +/- 0.24, and the B/F ratio from 1.78 +/- 0.22 to 2.90 +/- 0.30 (P less than 0.05 for both). In addition, the LH levels were measured during GnRH agonist treatment of ovarian carcinoma (n = 8), endometriosis (n = 8), and prostatic carcinoma after orchiectomy (n = 8). In the two former groups, serum B-LH decreased in 1 month to undetectable levels (less than 0.5 IU/L), and in the prostate cancer patients to 1.2 (0.8-1.9) IU/L (log mean and range of +/- SEM). The concomitant decline of I-LH was to 1.5-1.9 IU/L in the agonist-treated female patients, and that of F-LH to 0.10-0.15 IU/L; in the prostate cancer patients, respectively, these values were 7-8 and 0.3-0.7 IU/L. The B/I and B/F ratios during the agonist treatments could only be calculated in the prostate cancer patients (in the others, B-LH became undetectable). The B/I ratio decreased from 2.34 +/- 0.5 to 0.14 +/- 0.03 (P less than 0.01), but no suppression was found in the B/F ratio from a pretreatment value of 3.6 +/- 0.8. B-, I-, and F-FSH levels were measured in the GnRH agonist-treated orchiectomized prostate cancer patients. The pretreatment level of B-FSH was 154 (137-175), that of I-FSH was 38.0 (34.4-42.0), and that of F-FSH was 39.8 (35.3-44.9) IU/L. The B/I ratio of FSH was 3.76 +/- 0.49, and the B/F ratio was 3.53 +/- 0.59. The mean B-FSH level decreased during treatment by 87-93.5%, that of I-FSH by 98%, and that of F-FSH by 91.5% (P less than 0.01 for all).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The ratios of serum bioactive/immunoreactive luteinizing hormone and follicle-stimulating hormone in various clinical conditions with increased and decreased gonadotropin secretion: reevaluation by a highly sensitive immunometric assay. 214 Aug 31

Orchidectomy results in increased LH and FSH levels by removal of negative feedback at the hypothalamus and pituitary gland. However, the precise central nervous system mechanisms involved in elevation of gonadotropins after castration are unclear. We tested the hypothesis that catecholamine neuronal activity mediates the rise in serum LH that occurs after withdrawal of testosterone (T) negative feedback. The effects of acute and selective T withdrawal on brain catecholamine and LHRH activity and serum LH levels were determined in adult male rats. At the time of orchidectomy, rats were given sc implants of both T-containing and empty Silastic capsules. After recovery from surgery, the T-containing capsule was atraumatically removed from half of the animals (T-withdrawn), while the empty capsule was removed from the remaining rats (T-replaced). Rats were killed before and 6, 12, and 24 h after capsule removal. Serum T and LH levels were determined by RIA. Catecholamine content in microdissected nuclei of the LHRH neuronal system [medial preoptic nucleus, suprachiasmatic nucleus, retrochiasmatic area, arcuate nucleus (ARC), and median eminence (ME)] was measured by HPLC with electrochemical detection. Norepinephrine turnover rate was also determined in these areas by measuring the rate of decline of NE levels after blockade of synthesis with diethyldithiocarbamate. Additionally, LHRH content was measured by RIA within the ARC and ME. In T-replaced rats, the T capsules maintained serum T and LH levels within the normal range for intact male rats. In T-withdrawn rats, T levels fell into castrate range by 6 h after removal of the T capsule [0.12 +/- 0.04 ng/ml (mean +/- SEM); P less than 0.01 vs. T-replaced], and LH levels increased significantly from 0.23 +/- 0.04 ng/ml before capsule removal to 1.31 +/- 0.14 and 2.80 +/- 0.20 ng/ml 12 and 24 after T withdrawal, respectively (both P less than 0.01 vs. T-replaced). Despite a marked increase in serum LH levels, no significant changes in catecholamine content or NE turnover rate were observed in any of the hypothalamic nuclei of the LHRH neuronal system at any time after T withdrawal. ARC and ME LHRH levels also did not change significantly at any point after T withdrawal. These results suggest that activation of hypothalamic catecholamine neuronal activity is not required for the rise in serum LH levels after acute withdrawal of T negative feedback.
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PMID:Acute selective withdrawal of testosterone negative feedback increases luteinizing hormone secretion without altering hypothalamic catecholaminergic neuronal activity. 240 22

Although pharmacological doses of GnRH and TRH stimulate free alpha-subunit (alpha-subunit) secretion from the pituitary, little is known about the pattern and control of alpha-subunit release under physiological circumstances. Euthyroid men with idiopathic hypogonadotropic hypogonadism, a condition of deficient GnRH release, provide a unique opportunity to study alpha-subunit secretion before and during administration of a physiological regimen of GnRH administration. Before GnRH therapy, six euthyroid IHH men with normal endogenous TSH secretion had circulating alpha-subunit levels close to or below assay detection limits, with a mean level less than 0.5 ng/ml. During 12-42 weeks of physiological GnRH replacement, serum alpha-subunit concentrations rose to a mean value of 2.07 +/- 0.3 (+/- SEM) ng/ml (P less than 0.01). After GnRH administration, alpha-subunit was released in a pulsatile pattern following each dose of GnRH and mirrored the secretory pattern of LH. Increases in serum alpha-subunit concentrations during GnRH administration were closely correlated with increases in LH (r = 0.91; P less than 0.01), but not FSH (r = 0.24; P = NS), levels. In addition, a situation in which LH secretion was clearly predominant and FSH levels were barely detectable was created by increasing the frequency of GnRH administration to every 30 min. In this circumstance, free alpha-subunit concentrations increased in conjunction with LH levels in the face of decreased FSH levels. We conclude that replacement of GnRH regulates both the level and pattern of alpha-subunit secretion in GnRH-deficient men, and that there is tight correlation of alpha-subunit with LH, but not with FSH, secretion.
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PMID:Administration of low dose pulsatile gonadotropin-releasing hormone (GnRH) to GnRH-deficient men regulates free alpha-subunit secretion. 241 48

Processing of the 58 kDa to the 31 kDa form of inhibin (Inh) involves cleavage of the amino-terminal peptide (alpha N) from the alpha 43-subunit. We show that active immunisation of female sheep against a recombinant bovine alpha N impairs their fertility. In Exp 1, 5 treated (Group 1; 300 micrograms alpha N) and 6 control ewes (Group 2; adjuvant only) were immunized (Day 1) and given boosters on Days 22 and 56. In Group 1, mean +/- SEM binding of 125I-31 kDa Inh was less than 0.5% on Days 33 and 44, whereas binding of 125I-58 kDa Inh was 4.9 +/- 0.7 and 6.2 +/- 0.6%, respectively. In Group 2 binding of both tracers was less than 0.5%. The corpora lutea (CL)/ewe in Group 1 on Days 44 and 82 were 1.8 +/- 0.2 and 2.8 +/- 0.9, respectively, and were not different from those in Group 2 (1.7 +/- 0.3 and 1.5 +/- 0.2, respectively). One ewe in Group 1 versus 5/6 ewes in Group 2 were diagnosed pregnant. In Exp 2, 18 treated and 16 controls were immunized as in Exp 1. The binding of 125I-58 kDa Inh in treated ewes (2.4 +/- 0.3%) was greater than in controls (less than 0.5%) on Day 56. The CL/ewe in treated ewes (1.8 +/- 0.2) was similar to that in controls (2.0 +/- 0.1) on Day 76. All 16 control ewes but only 7/17 treated ewes were subsequently diagnosed pregnant. The plasma progesterone concentrations were similar in treated ewes which did (7.6 +/- 1.2 nmol/L) and did not (7.0 +/- 0.7) become pregnant. Neither basal nor GnRH-stimulated concentrations of LH, nor basal concentrations of Inh differed between treated and controls in Exp 2. Similarly, there were no differences in FSH, except that basal concentrations were higher in the luteal phase of treated ewes. We conclude that immunisation of ewes against alpha N results in a significant reduction in fertility.
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PMID:Immunisation against the amino-terminal peptide (alpha N) of the alpha 43 subunit of inhibin impairs fertility in sheep. 249 68

An important factor influencing the pregnancy rate after in vitro fertilization-embryo transfer (IVF-ET) appears to be the number of embryos transferred to the uterus. In this study, the influence of oocyte maturity and embryo quality on pregnancy rate was assessed in patients undergoing IVF-ET. Ovarian hyperstimulation was performed by human menopausal gonadotropin (hMG [n = 29]), clomiphene citrate (CC)/hMG (n = 81), and hMG/follicle-stimulating hormone (FSH [n = 13]) protocols. Oocyte maturity was graded on a scale from 1 to 5 based on the morphology of the ooplasm, cumulus mass, corona radiata, and membrana granulosa cells. Embryos were graded according to the symmetry of the blastomeres and the presence or absence of fragmentation. Mature preovulatory oocytes yielded the highest fertilization rates. No differences were found among the protocols in terms of fertilization rate, embryo quality, or pregnancy rate. When all protocols were combined, patients who conceived had a significantly higher number of embryos transferred than those who did not conceive (3.6 +/- 0.1 [mean = SEM] versus 2.7 +/- 0.1). When embryo quality was compared, there was no difference in the number of "B" embryos transferred between patients who conceived and those who did not (1.2 +/- 0.2 versus 1.2 +/- 0.1), but the patients who conceived had significantly more "A" embryos transferred (1.6 +/- 0.3 versus 0.8 +/- 0.1). These data suggest that the treatment protocol did not determine embryo quality. Furthermore, the increase in pregnancy rates seen with an increase in embryos transferred is the result of the transfer of more "A" embryos.
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PMID:The influence of oocyte maturity and embryo quality on pregnancy rate in a program for in vitro fertilization-embryo transfer. 250 52


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