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 has been suggested to play a role in gonadal feedback regulation of follicle-stimulating hormone (FSH) secretion; however, neither the half-life nor the time course of action of recombinant inhibin has been reported in any primate species. We sought to determine the disappearance half-life of circulating endogenous inhibin following castration in adult male monkeys, Macaca fascicularis, and to determine the half-life of administered recombinant human inhibin A and its effect on bioactive FSH and luteinizing hormone (LH) levels in castrate monkeys. Endogenous inhibin fell from 8,122 +/- 2,077 U/L (mean +/- SEM, n = 5) prior to castration to 383 +/- 84 U/L at 24 hours and 269 +/- 44 U/L at day 21 (P < 0.05 at 24 hours vs. day 21) (detection limit of assay 234 U/L). The early phase half-life of endogenous inhibin was 34 minutes (between 8 and 60 minutes) and a later phase half-life of 75 minutes was observed between 1 and 4 hours following castration. Recombinant inhibin exhibited a 14-minute early phase half-life between 8 and 60 minutes following the 5 micrograms intravenous (i.v.) recombinant inhibin dose, and a later phase half-life of 70 minutes between 1 and 4 hours in castrate monkeys (n = 3). Serum inhibin levels were maintained within or above the precastration range for 15 minutes. Single dose recombinant inhibin, 100 micrograms subcutaneous (SC) or intramuscular (IM) administered to castrate monkeys (n = 3), achieved and maintained normal serum inhibin levels for 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of castration and recombinant human inhibin administration on circulating levels of inhibin and gonadotropins in adult male monkeys. 805 35

The oral non-ergot D2-dopamine agonist quinagolide (CV 205-502, CAS 87056-78-8) has proven to be highly effective in suppressing elevated prolactin (PRL) levels. It was the aim of this study to search for possible interference of the drug with other endocrine systems which are partly under dopaminergic control, and to compare such effects to those of previously investigated prolactin inhibitors. Twelve patients suffering from macroprolactinoma were treated for at least 6 months with daily doses ranging from 50 up to 300 micrograms. During the first two months, individual doses were gradually increased either until serum PRL levels reached the normal range (n = 7) or until side effects made a further dose increase intolerable (n = 5). Mean basal PRL level fell from 255 +/- 65 (SEM) ng/ml before treatment to 19 +/- 8 ng/ml, after the definite dose was reached (p < 0.01). Luteinizing hormone (LH) rose from 0.6 +/- 0.8 (SD) to 1.7 +/- 1.6 mU/ml (p < 0.05). While basal levels of aldosterone, renin, follicle-stimulating hormone (FSH), triiodothyronine (T3), testosterone, and estradiol in females were not affected by the treatment, we found a significant rise in thyroxine (T4) and a decrease of estradiol in males. Blood pressure and renal clearances of creatinine, sodium, potassium, and chloride failed to show any significant change. Following stimulation with metoclopramide, aldosterone and renin rose sharply before treatment was initiated. When the test was repeated during treatment, the increase of plasma renin was slightly dampened, whereas the rise of aldosterone remained unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of macroprolactinoma with the new potent non-ergot D2-dopamine agonist quinagolide and effects on prolactin levels, pituitary function, an the renin-aldosterone system. Results of a clinical long-term study. 809 4

Following a femoral neck fracture and vertebral compression fractures in two patients with severe haemophilia A, bone density and turnover were measured in 19 males with severe haemophilia A (all HIV negative, 18/19 hepatitis C antibody positive) and in 19 age/sex matched controls. Bone density at the lumbar spine (L2-4), measured by dual energy X-ray absorptiometry, was significantly lower in the haemophiliac patients (HPs) at (mean +/- SEM) 1.109 +/- 0.042 g/cm2 vs. 1.234 +/- 0.027 in controls; p = 0.018. Femoral neck density was also lower at 0.877 +/- 0.034 g/cm2 (HPs) vs. 1.067 +/- 0.032; p < 0.0005. No significant differences were evident between the groups for serum calcium, parathyroid hormone, luteinizing hormone, follicle-stimulating hormone or 1,25 dihydroxyvitamin D3, nor for fasting urinary hydroxyproline, pyridinoline or deoxypyridinoline excretion. Serum total alkaline phosphatases was elevated in HPs at 200 +/- 10 U/l vs. 158 +/- 8; p = 0.004. Similarly, gamma-glutamyl transferase was elevated at 42 +/- 7 U/l (HPs) vs. 20 +/- 2; p = 0.007. Serum total testosterone and sex-hormone-binding globulin (SHBG) were higher in HPs at 26 +/- 2.5 nmol/l vs. 17.4 +/- 1.6 (p = 0.009) and 56 +/- 6 nmol/l vs. 27 +/- 3 (p = 0.0005), respectively. Free androgen index, however, was lower in HPs at 44 +/- 5 vs 69 +/- 7; p = 0.008. These results suggest significant osteopenia associated with haemophilia A. This may be partly due to liver dysfunction in HPs, but other factors, e.g. relative immobilization, may also be relevant.
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PMID:Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study. 820 6

Two experiments were conducted in cyclic beef heifers to determine whether active immunization against bovine inhibin alpha 1-26 Gly-Tyr (bINH) affected follicular dynamics, hormone concentration or ovulation rate. In Expt 1, heifers (n = 9) were actively immunized against bINH conjugated to human alpha globulins (HAG) using bis-diazotized benzidine in non-ulcerative Freund's adjuvant (NUFA; primary on day 0; booster injections on days 53, 84 and 116 using conjugated bINH and on days 176 and 366 using unconjugated bINH; ten heifers were used as controls). Ovaries were examined daily using ultrasound scanning (days 70-155 and 384-391) and corresponding blood samples were collected for bINH antibody titre, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and oestradiol determinations. Four treated and four control heifers were injected with 10 micrograms gonadotrophin-releasing hormone (GnRH) on day 386 (day 2 of the oestrous cycle). Although bINH-immunized heifers had variable antibody titres ranging from 4 to 50% I125-labelled bINH bound to serum diluted 1:2000, ovulation rate was unaffected. In oestrous cycles with three dominant follicles, the ovulatory follicles grew faster (2.5 +/- 0.2 versus 1.6 +/- 0.3 mm day-1; mean +/- SEM), had shorter durations of growth (5.7 +/- 0.8 versus 9.6 +/- 1.6 days) and duration of detection (7.5 +/- 0.8 versus 12.0 +/- 2.4 days) in immunized heifers. Mean concentrations of FSH, LH and oestradiol were unaltered in most cases during oestrous cycles in bINH-immunized compared with control heifers. There was no significant difference in the percentage increase in FSH or LH, after GnRH injection, between control and immunized heifers. As ovulation rate was unaltered in the first experiment, a second similar study was designed using a different immunization protocol. In Expt 2, heifers were immunized with bINH conjugated to human serum albumin using glutaraldehyde with the following doses: 0.0 (control; n = 7), 0.33 (n = 7), 1.0 (n = 8) and 3.0 (n = 7) mg. Three booster immunizations were given 33, 66 and 209 days after primary immunization. Immunization increased the number of oestrous cycles with multiple ovulations (42 of 132 (32%) oestrous cycles examined) compared with controls (1 of 30 (3.3%) oestrous cycles examined). Neither titre nor ovulation rate was affected by dose of bINH used. In summary, following bINH immunization, ovulation rate was not increased despite changes in follicular dynamics in Expt 1, but was increased in 32% of oestrous cycles in Expt 2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Active immunization of heifers against a synthetic fragment of bovine inhibin. 846 14

Gonadotrophin surge-attenuating factor (GnSAF) is a putative nonsteroidal ovarian factor that attenuates the luteinizing hormone (LH) surge in superovulated women. GnSAF bioactivity was studied during the luteal phase by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. In both cycles, the pituitary response to an acute intravenous injection (10 micrograms) of luteinizing-hormone-releasing hormone (LHRH) was investigated in late follicular (follicle size 16 mm), early luteal (day 5 after human chorionic gonadotrophin, hCG), midluteal (day 9 after hCG) and late luteal phase (day 12 or 13 after hCG). FSH was injected daily at the dose of 225 iu on cycle days 2, 3 and 4, and 150 iu thereafter. The increase in LH and FSH (mean +/- SEM) 30 min after LHRH in the spontaneous cycles decreased significantly from early to late luteal phase and remained unchanged in the FSH-treated cycles. Increases in LH and FSH 30 min after LHRH were significantly attenuated in the FSH-treated compared with the spontaneous cycles in late follicular and luteal phases. Serum oestradiol and progesterone concentrations were significantly higher in the FSH than in the spontaneous cycles only in early, but not in mid- and late luteal phase. The pattern of serum oestradiol and progesterone changes during the luteal phase did not correlate with the increases in LH and FSH 30 min after hCG both in the spontaneous and the FSH cycles. These results suggest that GnSAF bioactivity is high during the luteal phase of superovulated cycles.
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PMID:Activity of gonadotrophin surge-attenuating factor during the luteal phase in superovulated women. 846 20

Transforming growth factor alpha (TGF alpha) is implicated as a paracrine growth factor in the regulation of human granulosa cell function. To investigate this further, we have examined the actions of TGF alpha on the basal and follicle-stimulating hormone (FSH)-stimulated aromatase activity of human granulosa cells to determine how this growth factor influences oestrogen biosynthesis in the follicle. Granulosa cells from women having in-vitro fertilization during untreated or gonadotrophin-stimulated cycles were cultured for 1-6 days in the presence or absence of FSH or TGF alpha at a range of doses. Aromatase activity, expressed as oestradiol production, was determined after culture during a 3 h test period. After 2 days, TGF alpha (1-300 ng/ml) decreased basal and FSH-stimulated aromatase activity in a dose-dependent manner (ED50 = 3 ng/ml). In contrast, after 4 days, TGF alpha enhanced both basal and FSH-stimulated aromatase activity. Repeated experiments revealed a consistent pattern of inhibition on day 2, which was more marked in the presence of FSH (reduction by 30.6 +/- 9.1%, mean +/- SEM; n = 14; P < 0.01), and stimulation on day 4 in both the absence (increased by 61.4 +/- 20.6%, mean +/- SEM; n = 6; P < 0.05) and presence of FSH (increased by 36.0 +/- 15.2%, mean +/- SEM; n = 8; P < 0.05). The results provide further evidence that TGF alpha is a paracrine factor in the control of oestrogen biosynthesis, but the actions can be either inhibitory or stimulatory depending on the duration of exposure.
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PMID:Time-dependent effects of transforming growth factor alpha on aromatase activity in human granulosa cells. 856 69

Melatonin, the hormone of the pineal gland, which in animal studies has been found to inhibit aging processes, is secreted in smaller amounts towards senescence. Menopause, an aging process in women, is known to be associated with typical changes in gonadotropin and sex steroid secretion. Our main objective was to study the possible role of melatonin in the hormonal regulation of menopause. This study focused on detailed changes in melatonin and follicle-stimulating hormone (FSH) secretion cross-sectionally in pre- to postmenopausal females. Special attention was paid to females aged around 50 years, which is the mean menopausal age. Seventy-seven healthy female volunteers aged 30-75 years were the subjects of this study. Melatonin was measured radioimmunologically from nocturnal urine collected between 20.00 and 08.00 h, and FSH and melatonin from blood samples taken at 0.900 h. Nocturnal urinary excretion of melatonin was found to decline significantly from premenopause to postmenopause. The youngest premenopausal women (age group 30-39 years) excreted the highest amounts of melatonin (21.2 +/- 2.2 pmol/h, mean +/- SEM, N = 17). In the age group 40-44 years the excretion declined by 41% (p < 0.05). The second significant decline (35%, p < 0.05) took place between the age groups 50-54 years and 55-59 years. A declining trend as a function of age was also seen in morning serum melatonin. Serum FSH rose sharply to high levels before the age of 50 (p < 0.01) and remained at a high level thereafter. Urinary melatonin correlated negatively with serum FSH (r = -0.32, p < 0.05). In conclusion, the inverse changes in melatonin and FSH secretion during the perimenopausal years, with the sharpest decline in nocturnal excretion of melatonin far before menopause, suggest that melatonin may be permissively linked to the initiation of menopause.
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PMID:Decrease in melatonin precedes follicle-stimulating hormone increase during perimenopause. 881 Jul 31

Manipulation of diet is known to affect the secretion of the gonadotropins and growth hormone (GH). The former are under the direct regulation of hypothalamic gonadotropin-releasing hormone (GnRH) and the latter is under the dual control of GH-releasing hormone (GHRH) and somatostatin (SRIH). At the level of the hypothalamus, both galanin (GAL) and neuropeptide Y (NPY) are thought to regulate the secretion of the above releasing and inhibiting factors. Both peptides are also potent orexigenic agents. We have studied ovariectomised ewes that were either well-fed (HIGHs) or underfed (LOWs) and used immunocytochemistry and image analysis to measure the levels of GAL and NPY in hypothalamic nuclei in which GnRH, GHRH and SRIH are found and which are also involved in the regulation of appetite and feeding. The sheep were given a normal diet or a restricted diet for 15 months. Four pairs of ewes were then blood-sampled to measure GH, luteinising hormone (LH), and follicle-stimulating hormone (FSH) and then killed for recovery of the brains. After perfusion, cryostat sections were cut through the entire hypothalamus, mounted, and stained fro NPY or GAL. All treatments and analyses were performed in pairs. The number of immunoreactive cells, density of terminals and total immunoreactivity (IR) were quantified by image analysis by sampling 6-16 subareas (depending on region) on sections through the pre-optic area (POA), paraventricular nucleus (PVN), arcuate nucleus (ARC) and median eminence (ME). Mean (+/- SEM) live weight of the LOWs was significantly (p < 0.0001) lower than that of the HIGHs (37.6 +/- 0.6 kg vs. 60.6 +/- 0.5 kg). There was no difference in the plasma levels of LH and FSH but the area under the GH curve (ng/ml/h) was significantly (p < 0.0001) greater in the LOWs (320 +/- 40.9 vs. 67.3 +/- 16.1). There was an increased number of cells staining for NPY but not GAL in the ARC/ME of the LOWs. Nevertheless, the oveall level of immunostaining for both peptides was increased in the LOWs. GAL IR was restricted to the mediobasal hypothalamus. In the LOWs, the density of NPY terminal fields in each area of the ARC was significantly (p < 0.05) increased. Food restriction also increased the density of NPY terminals in the POA and PVN (p < 0.025) but not in the ME. These data indicate that a dietary manipulation which affects GH secretion but not the gonadotropins may be mediated by NPY and GAL neuronal systems in specific brain regions within the hypothalamus.
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PMID:Increased galanin and neuropeptide-Y immunoreactivity within the hypothalamus of ovariectomised ewes following a prolonged period of reduced body weight is associated with changes in plasma growth hormone but not gonadotropin levels. 887 37

We developed an assay system for measuring free follistatin by using an anti-follistatin mouse monoclonal antibody and [125I]activin A. The sensitivity of this assay was 0.5 microgram/l and cross-reactivities with inhibin, luteinizing hormone, follicle-stimulating hormone and growth hormone were all less than 0.5%. The dose-response curves of human sera and follicular fluid were parallel to the standard curve, and the follicular fluid contained a large amount of follistatin (6.4 +/- 0.5 mg/l, mean +/- SEM; N = 13). The within- and between-assay coefficients of variation calculated from the analysis of serum samples of four different concentrations were 3.3-7.8% and 3.9-11.0%, respectively. The recovery rates of free follistatin at five different doses were 86.4 - 102.4%. When activin A was added to the same sample, free follistatin recovery rate declined dose-dependently. Gel filtration analyses of human serum and follicular fluid resulted in a single peak corresponding to authentic follistatin. Using this assay, free follistatin concentrations in sera were measured in normal, pregnant and diseased subjects. The free follistatin level in serum of normal adults was 3.5 +/- 0.2 micrograms/l (N = 60), which was significantly elevated in pregnant women (16.7 +/- 1.3 micrograms/l, N = 56), and in patients with chronic liver disease (8.1 +/- 1.1 micrograms/l, N = 20), chronic renal failure (6.7 +/- 0.9 micrograms/l, N = 42), advanced solid cancer (8.5 +/- 1.0 micrograms/l, N = 39) and hematological malignancies (6.8 +/- 1.0 micrograms/l, N = 18). These data indicated that the free follistatin concentration in serum is detectable and varies during pregnancy and in various diseased states.
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PMID:Determination of free follistatin levels in sera of normal subjects and patients with various diseases. 889 Jul 27

The secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is regulated by gonadotropin-releasing hormone (GnRH). As men age, mean serum concentrations of immunoreactive gonadotropic hormones tend to increase, while serum testosterone concentrations tend to decline. To evaluate age-related changes in gonadotroph cell function, we have assessed the dose-dependent secretory responses of immunoreactive LH, FSH and alpha-subunit to saline versus five doses of GnRH in older and young men. Ten older men, mean age 66 years (range 61-78), and nine young men, mean age 26 years (range 22-30), received iv bolus injections of GnRH (range 10-100 micrograms) in randomized order every 2 h, except that the 100-microgram dose was always given last. Blood samples for immunoradiometric assays of serum LH, FSH and alpha-subunit concentrations were obtained every 10 min for a total of 12 h, which included a 2-h preinjection baseline. Deconvolution analysis was performed to estimate gonadotropin and alpha-subunit secretory burst mass, amplitude and duration, as well as endogenous LH, FSH and alpha-subunit half-lives. The mean (+/- SEM) baseline 2-h serum FSH (IU/I) concentration was higher in older than younger men (5.9 +/- 0.8 vs 3.8 +/- 0.5, p < 0.05). The mean 2-h serum LH concentrations after GnRH were significantly higher than corresponding values in young men at GnRH doses of 25, 50 and 75 micrograms, and in the case of FSH at GnRH doses of 10 and 25 micrograms. Non-linear curve-fitting of these dose-response relationships revealed that the calculated maximal mean 2-h serum LH concentration response (IU/l) was higher in older than young men following GnRH stimulation: 15.4 (13.5-16.2) vs 10.8 (8.7-12.1) (95% confidence interval). The maximal mean 2-h serum FSH concentration response (IU/l) was also significantly higher in older men: 11.9 (10.2-13.1) versus 8.6 (7.2-9.6). Maximal alpha-subunit responses (microgram/l) were similarly increased in the older cohort: 1.16 (0.99-1.25) vs 0.83 (0.71-0.91). The incremental LH (p < 0.05) and FSH (p < 0.01) secretory burst mass from 10 to 25 micrograms GnRH was significantly greater in older than younger men. The LH and FSH half-lives and second component alpha-subunit half-lives were similar in older and young men. In addition, secretory burst durations were invariant of age. In contrast, by non-linear curve-fitting, the calculated mass of LH secreted was higher in older men at 13.5 (11.8-15) vs 10.6 (9.2-11.7) IU/l of distribution volume (p < 0.05) for the maximal absolute mass and 11.3 (9.5-12.7) vs 7.4 (6.0-8.4) IU/l (p < 0.05) for the maximal incremental mass of LH secreted after GnRH. The estimated maximal mass of FSH secreted after GnRH also was higher in older men: 4.6 (3.4-5.5) vs 3.2 (2.9-3.4) IU/l (p < 0.01). Finally, calculated maximal GnRH-stimulated alpha-subunit secretory burst mass was statistically greater in older individuals: 2.3 (1.8-2.5) vs 1.6 (1.4-1.8) micrograms/l. In contrast, half-maximally effective GnRH doses were not different in the two age groups. We conclude that older men show significantly increased maximal and incremental gonadotropin release due to amplified secretory burst mass in response to escalating doses of GnRH with no evident differences in LH, FSH, or alpha-subunit half-lives or secretory burst durations. Increased gonadotroph responsiveness may be due to diminished gonadal hormone negative feedback or primary alterations in the hypothalamo-pituitary unit with aging.
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PMID:Contrasts in the gonadotropin-releasing hormone dose-response relationships for luteinizing hormone, follicle-stimulating hormone and alpha-subunit release in young versus older men: appraisal with high-specificity immunoradiometric assay and deconvolution analysis. 892 20


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