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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our research programs required the preparation of hypophysectomized and orchidectomized rhesus monkeys. This afforded us the possibility to characterize and compare levels of the gonadotropin and inhibin subunit mRNAs in pituitaries from intact and castrate monkeys. Eighteen adult male monkeys, four of which had been bilaterally orchidectomized 5-9 months previously, were used in this study. Plasma concentrations of LH and FSH were, respectively, 188.5 +/- 5.3 and 246.8 +/- 25.2 ng/ml in the castrate monkeys and 25.8 +/- 4.5 and 4.1 +/- 1.1 ng/ml (mean +/- SEM) in the intact animals. Total pituitary RNA was hybridized to cDNA probes for cynomolgus monkey gonadotropin subunits (FSH beta, LH beta, and the common alpha-subunit) and for human inhibin subunits (alpha, beta B, and beta A) by Northern blot analysis, and mRNA levels were normalized by subsequent hybridization to cyclophilin. Each of the gonadotropin subunit probes hybridized to a single RNA species with the approximate sizes of 1.6 kilobases (kb; FSH beta), 0.7 kb (LH beta), and 0.8 kb (alpha). Levels of LH beta and alpha-subunit mRNAs in pituitaries from castrate monkeys were about 5- and 2-fold higher, respectively, than those in pituitaries from intact monkeys. FSH beta mRNA, on the other hand, was elevated about 27-fold in castrate monkeys [mean +/- SEM, 3176 +/- 408 cpm bound (n = 4 castrate) and 116 +/- 30 cpm bound (n = 8 intact]). Inhibin beta B-subunit mRNA was present in the monkey pituitary as a doublet of about 5 kb, and it was approximately twice as abundant in intact pituitaries as in castrate pituitaries. Hybridizations involving inhibin beta A cDNA revealed a faint band in the region expected for monkey beta A mRNA (6.5 kb) in three of six RNA samples from intact monkeys and a 0.3- to 0.4-kb mRNA species. mRNA encoding the inhibin alpha-subunit was undetectable by Northern blot hybridization. These results indicate that the postpubertal testis imposes an inhibition on the expression of the genes encoding FSH beta, LH beta, and glycoprotein hormone alpha-subunit and that this suppression of the FSH beta gene in the monkey is much greater than that in the rat. In addition, the monkey pituitary may be a source of activin, which may act locally to modulate FSH gene expression and secretion.
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PMID:Effects of orchidectomy on gonadotropin and inhibin subunit messenger ribonucleic acids in the pituitary of the rhesus monkey (Macaca mulatta). 153 90

Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P < 0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy.
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PMID:Hypertension in pregnancy: changes in activin A maternal serum concentration. 747 15

Rat pituitary cells express messenger RNA for the activin-binding protein, follistatin (FS), and rat and bovine pituitary cell cultures secrete FS into the medium. In the present study, a previously validated, heterologous RIA for ovine FS was employed to investigate FS synthesis, secretion, and regulation in cultures of ovine anterior pituitary cells. The validity of the RIA was confirmed by the finding that FS immunoreactivity in ovine pituitary cell culture-conditioned medium diluted in parallel with purified bovine FS, and fractionation of the conditioned medium resulted in the coelution of activin-binding activity with the FS immunoactivity. The concentration of endogenous ovine FS achieved in the culture medium (0.08-0.6 nM) was in the range over which bovine FS suppresses FSH secretion in these cultures (IC50 = 0.5 nM). To characterize the relationship between endogenous FS and FSH secretion, dispersed ovine pituitary cells were preincubated with 10% fetal bovine serum for 2 days, then cultured between days 2-5 in the presence of a chemically defined serum substitute. Under these conditions, FS was continuously secreted at a rate of 12.1 +/- 1.8 ng/10(6) cells.day (mean +/- SEM; n = 18), whereas FSH was secreted at 64 +/- 13 ng/10(6) cells.day (n = 7). The secretion of FS and FSH changed in a reciprocal way as culture conditions were altered either by maintaining exposure of the cells to fetal bovine serum or by plating the cells at a 6- to 10-fold higher seeding density. Under the latter circumstance, for instance, FS secretion during the 3-day test period decreased to 47 +/- 14% (n = 10) and FSH secretion increased to 137 +/- 6% (n = 6) of the respective values in cultures of dispersed cells. FS secretion was increased nearly 3-fold (P < 0.05) in a dose-dependent manner by continuous exposure of ovine pituitary cells between days 2-5 to recombinant human activin A (1-10 nM), which concomitantly increased FSH secretion. Recombinant human inhibin A (0.003-10 nM); the synthetic glucocorticoids, RU28362 and dexamethasone (each 1-100 nM); the sex steroids, testosterone (1-100 nM), 17 beta-estradiol (0.001-5 nM), and progesterone (4-2500 nM); and the vitamin A derivative, retinoic acid (0.3-32 microM), each inhibited FSH secretion from these cultures, but only the last agent significantly (P < 0.05) increased FS secretion. Inhibin prevented the stimulation of FSH secretion by activin A without affecting its stimulation of FS secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ovine anterior pituitary production of follistatin in vitro. 766 60

The expression of the mRNA for the inhibin/activin subunits (alpha and beta A) in the granulosa layer of the five largest preovulatory follicles of the hen was investigated. Total RNA from the granulosa layer of the F5 (the fifth largest) to F1 (the largest) follicles was extracted and analyzed by Northern blot analysis using homologous chicken inhibin alpha and beta A subunit cDNA probes. RNA loading was quantified by a cDNA probe of bovine 18S rRNA. Results showed that for the chicken inhibin alpha subunit mRNA signals (n = 3), the mean relative intensity for the F1, F2, F3, and F4 follicles was 0.50 +/- 0.10 ( +/- SEM,), 0.52 +/- 0.08, 0.59 +/- 0.06, and 0.81 +/- 0.04, respectively, compared to a mean relative intensity of 1.00 (p < 0.05) for the F5 follicle. For the beta A subunit mRNA signals (n = 3), the mean relative intensity for the F5, F4, F3, and F2 follicles was 0.25 +/- 0.06, 0.28 +/- 0.15, 0.40 +/- 0.17, and 0.48 +/- 0.10 (p < 0.05) for the F1 follicle. The inhibin alpha subunit was also estimated to be more abundantly expressed among follicles in the granulosa layer than was the beta A subunit. Our data indicate that the expression of inhibin alpha and beta A subunits is differentially regulated in the hen granulosa layer during follicular development. Expression of the alpha subunit is reduced with follicular development whereas inhibin beta A subunit expression is dramatically enhanced. In addition, the granulosa layer of the large preovulatory follicles may produce more inhibin alpha subunit than beta A subunit, and the F1 follicle may be the primary source of the beta A subunit for dimeric inhibin and/or activin in the hen.
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PMID:Expression of inhibin alpha and inhibin/activin beta A subunits in the granulosa layer of the large preovulatory follicles of the hen. 882 54

The aim of the present study was to determine the characteristics of activin A secretion in women with normal and abnormal pregnancy. With this purpose, a prospective study was done to evaluate the putative pulsatile pattern of serum activin A in serial specimens of blood collected during a certain amount of time (every 15 min for 3 h). A group of pregnant women (N = 24) participated in a cross-sectional study. They were subdivided into three groups: healthy pregnant women (N = 8), patients with preterm labor (N = 8) and patients with gestational diabetes (N = 8) before and after insulin therapy. Secretory pulses of serum activin A were determined in all patients with a specific frequency and amplitude by using two different computerized analyses, i.e. DETECT and CLUSTER. Mean +/- SEM values of serum activin A were significantly higher in patients with preterm labor and gestational diabetes than in controls (p < 0.01), showing a significant decrease following insulin therapy in diabetic patients (p < 0.01). Specific pulses of serum activin A levels were observed in all women. The mean pulse frequency did not change significantly between healthy controls and the different pathological groups. Patients with gestational diabetes after insulin therapy showed a pulse frequency that was significantly higher than in controls (p < 0.05). When the mean peak amplitude of activin A pulses was evaluated, patients with preterm labor or gestational diabetes showed values that were significantly higher than in healthy pregnant women (p < 0.01) A significant, inverse correlation between pulse frequency and amplitude was found both in healthy pregnant women (p < 0.05) and in patients with gestational diabetes (p < 0.001). The present study showed that circulating activin A levels in pregnant women change in a pulsatile pattern whose pulse amplitude is modified in the presence of gestational diseases, such as preterm labor or gestational diabetes.
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PMID:Episodic secretion of activin A in pregnant women. 889 Jul 26

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

We developed and validated a RIA for measuring serum activin A. The least detectable value of this assay was 0.1 micrograms/L, and the antibody used cross-reacted slightly with bovine inhibin (3.2%) and porcine activin AB (10.0%) but not with porcine activin B (< 0.5%). Serum activin A was extracted with acetonitrile and trifluoroacetic acid to get rid of the interaction with possible binding proteins in serum. As a result of this extraction procedure, the dose-response curve of serum extract was parallel to the standard curve and a single immunoreactive (ir-) peak was demonstrated on gel chromatographic analysis with constant recovery rates over 80%. Serum ir-activin A level in healthy adults was 1.27 +/- 0.03 micrograms/L (mean +/- SEM, n = 180); being 1.38 +/- 0.05 micrograms/L (n = 90) in male, and 1.16 +/- 0.05 micrograms/L (n = 90) in female subjects, with a tendency to increase with age. Serum ir-activin A level during pregnancy showed a marked increase with the advance of gestation; 1.65 +/- 0.41 micrograms/L (n = 7) in the early, 4.50 +/- 1.13 micrograms/L (n = 21) in the middle, and 16.32 +/- 2.25 micrograms/L (n = 26) in the late trimester, with a rapid decline after delivery. On the other hand, serum ir-activin A level was elevated in patients with hyperthyroidism (1.91 +/- 0.37 micrograms/L, n = 31), liver cirrhosis (2.03 +/- 0.71 micrograms/L, n = 10), chronic renal failure (3.41 +/- 0.34 micrograms/L, n = 41), and advanced solid cancer (2.24 +/- 0.52 micrograms/L, n = 67). These findings indicate that serum ir-activin A level varies with physiological conditions such as aging and pregnancy, and that it may reflect the altered production and metabolism of activin A in certain diseased conditions.
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PMID:Serum immunoreactive activin A levels in normal subjects and patients with various diseases. 896 39

Activin A and inhibin B levels were measured, using a two-site enzyme immunoassay, in extra-embryonic coelomic fluid, amniotic fluid and maternal serum samples retrieved from 23 healthy pregnant women, at 8 (n=8), 9 (n=8), and 10 (n=7) weeks of gestation. Dimeric activin A and inhibin B were measurable in all samples. Median (+/-SEM) activin A concentrations in coelomic fluid (0.98+/-0.34 ng/ml) were significantly higher than in maternal serum (0.68+/-0.05 ng/ml) and in amniotic fluid (0.09+/-0.04 ng/ml) (P<0.05). Maternal serum activin A levels were significantly higher than amniotic fluid concentrations. Median (+/-SEM) inhibin B concentrations in coelomic fluid (24.32+/-6.02 pg/ml) were significantly higher than in maternal serum (5.94+/-0.97 pg/ml) and in amniotic fluid (6.31+/-1.53 pg/ml) (P<0.05), while no significant difference between maternal serum levels and amniotic fluid concentrations was found. No significant difference in activin A and inhibin B levels in extra-coelomic fluid, amniotic fluid, and maternal serum throughout the 3 weeks of pregnancy was found. The present study showed that coelomic fluid is an important reservoir of activin A and inhibin B, supporting the hypothesis that the extra-embryonic coelom may have a secretory role during the first 11 weeks of gestation.
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PMID:Activin A and inhibin B in extra-embryonic coelomic and amniotic fluids, and maternal serum in early pregnancy. 969 66

Follistatin is a specific binding protein which controls bioavailability of activins and inhibins which have an important role in fetal development. In the first trimester of pregnancy bioactive dimeric inhibins are found at high concentrations in the extra-embryonic coelomic fluid, but the distribution of follistatin and activins is not known. We have used recently developed immunoassays for follistatin, activin A and activin AB to determine their presence in the intrauterine compartments during early pregnancy. Follistatin was present in highest concentrations in the extra-embryonic coelomic fluid (11.72 +/- 1.70 ng/ml; median +/- SEM), with less in maternal serum (6.35 +/- 4.58) and lowest amounts in amniotic fluid (0.97 +/- 0.52). Follistatin concentrations in extra-embryonic coelomic fluid were highly correlated with both dimeric inhibin isoforms. Activin A was present in only barely detectable amounts in some samples of extra-embryonic coelomic fluid (41% of samples) and maternal serum (26%) and was undetectable in all amniotic fluid samples. Activin AB was undetectable in all compartments. The presence of follistatin in the amniotic and extra-embryonic coelomic fluids may regulate the availability of bioactive activins and inhibins which are released into the intrauterine compartments during the development of the fetus and placenta in early pregnancy.
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PMID:Follistatin and activin A in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy. 980 96

Familial polycystic ovarian syndrome (PCOS) has been proposed to be linked to a site near the follistatin gene. We studied the concentrations of circulating follistatin, activin A and inhibin B in well-characterized subjects with PCOS (n = 108) and controls without PCOS (n = 20). Mean (+/- SEM) concentrations of follistatin were higher (P < 0.05) in PCOS (0.27 +/- 0.03 ng/ml) than controls (0.15 +/- 0.02 ng/ml) and activin A were lower (P < 0.05) in PCOS (0.20 +/- 0.01ng/ml) than controls (0.24 +/- 0.02 ng/ml). Inhibin B concentrations were not different between the two groups: PCOS (0.06 +/- 0.01ng/ml), and controls (0.06 +/- 0.01ng/ml). It is proposed that higher concentrations of follistatin with lower concentrations of activin A may relate to follicular development not proceeding beyond 8-10 mm and may be partly responsible for the lack of pre-ovular follicle development in PCOS.
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PMID:Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome. 1127 15


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