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PubMed1996

Inhibin A and inhibin B are inversely correlated to follicle-stimulating hormone, yet are discordant during the follicular phase of the rat estrous cycle, and inhibin A is expressed in a sexually dimorphic manner.

Inhibin A and inhibin B are related dimeric protein hormones and endocrine regulators of the reproductive axis. Specifically, inhibin inhibits FSH secretion from the anterior pituitary. The inhibins are synthesized by the gonads and are themselves modulated by FSH. Although the activity of these ligands has been well characterized, the circulating concentrations of dimeric inhibin A and dimeric inhibin B have not previously been reported for the rat. Our group examined the serum concentration of inhibin A and inhibin B in normally cycling female rats, male rats, and in gonadectomized animals. Both inhibin isoforms are detected in intact female rat serum. Interestingly, inhibin B, but not inhibin A, is detected in intact male rat serum. Neither inhibin isoform is detected in long-term castrate female or male rats. In normally cycling female rats, inhibin A was low on the morning of metestrus and rose steadily to a peak on proestrus. In contrast, inhibin B was elevated on the mornings of metestrus, diestrus, and proestrus. Both ligands persisted in the serum until proestrus evening. Serum inhibins then declined beginning at 2100 h (inhibin A) or 1800 h (inhibin B) on proestrus, and the concentrations reached a nadir on the morning of estrus (0600 h). The nadir coincided with the peak of the secondary FSH surge. Both inhibins rebounded later on the morning of estrus. The results of this study demonstrate that dimeric, ovarian-derived inhibin A and inhibin B circulate in the female rat. The inverse relationship of the inhibins during the secondary FSH surge is consistent with the hypothesis that they participate in the regulation of reproductive cyclicity. The differing patterns of inhibin A and inhibin B during the period of follicular development on metestrus and diestrus suggest different follicle sources or regulation of these molecules during this period. We further demonstrate that inhibin B is the dominant form of FSH regulating protein in the male rat.

Animals↗

PubMed1996

Second trimester levels of maternal serum inhibin A, total inhibin, alpha inhibin precursor, and activin in Down's syndrome pregnancy.

OBJECTIVE: To determine the levels of various biochemical forms of the placental protein, inhibin (total inhibin, inhibin A, and alpha inhibin precursor) and activin in maternal serum samples from fetal Down's syndrome, and to determine which of these analytes most effectively identifies samples from affected pregnancies. METHODS: Maternal serum samples were collected from 100 unaffected pregnancies and 20 cases of fetal Down's syndrome during gestational weeks 15-20 for routine triple marker screening, and were stored frozen after clinical assay. Levels of inhibin A, total inhibin, alpha inhibin precursor (pro-alphaC), and activin were compared retrospectively in the Down's syndrome cases and control samples. RESULTS: There was no association of the inhibin or activin levels with gestational age or length of freezer storage, and therefore single median values were determined for the unaffected pregnancies for each analyte. Multiples of the unaffected median (MoM) values were calculated for all cases, showing that inhibin A (1.95 MoM) provided the best discrimination between cases and controls, followed by total inhibin (1.37 MoM). Mann-Whitney U analysis showed significant group differences in inhibin A (P = 0.0001) and total inhibin (P = 0.0005). In contrast, alpha inhibin precursor (0.81 MoM) and activin (1.16 MoM) levels in Down's syndrome cases were not significantly different from those in unaffected patients. CONCLUSIONS: Levels of inhibin A and total inhibin, but not alpha inhibin precursor or activin, are significantly raised in maternal serum from cases of fetal Down's syndrome. These data, taken together, indicate that inhibin A levels are specifically raised in Down's syndrome pregnancy. 45% of the inhibin A levels in the Down's syndrome samples were above the 90th centile of unaffected levels, indicating that inhibin A may be as good a marker as human chorionic gonadotrophin, the most informative serum marker currently in use.

Activins↗

PubMed1997

Ontogeny of inhibin secretion in the rat testis: secretion of inhibin-related proteins from fetal Leydig cells and of bioactive inhibin from Sertoli cells.

The ontogeny of inhibin secretion in the testis of rats was investigated. Testicular localization, content of immunoactive and bioactive inhibin and its molecular size in fetal and neonatal rats (from 16 days of gestation to 5 days of age) were determined. Strong immunostaining with an antiserum against a polypeptide of porcine inhibin alpha-subunit was noted in testicular interstitial cells from 16 days of gestation. Co-localization of inhibin alpha-subunit and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was observed in the interstitial cells until 2 days of age. Immunoreactive inhibin alpha-subunit in the interstitial tissue had disappeared by 5 days of age, although 3 beta HSD-positive cells were still detected. Weak immunostaining for the inhibin alpha-subunit was detected in the seminiferous tubules, probably in the cytoplasm of Sertoli cells, from 20 days of gestation onward. No inhibin alpha-subunit immunostaining was observed in germ cells throughout the experimental period. Testicular inhibin was detected at 16 days of gestation (49.5 +/- 6.7 pg per testis) by RIA. Testicular immunoreactive inhibin showed a tendency to increase during fetal life and levels were maintained at a similar value after birth (697.0 +/- 46.9 pg per testis at 5 days of age). Inhibin bioactivity and its molecular size in testicular homogenate was examined at 17 days of gestation and 0 and 5 days of age. Although no bioactivity was detected at 17 days of gestation, bioactivity was noted at 0 and 5 days of age (177.7 and 1303.9 pg per testis respectively). Immunoblot analysis with antiserum against inhibin alpha-subunit revealed only approximately 40 kDa molecular masses in the testis at 17 days of gestation, probably inhibin-related proteins, but not inhibin. At 0 and 5 days of age, a protein of 30 kDa molecular mass, possibly inhibin, was detected as well as material of approximately 40 kDa molecular mass. FSH in the plasma was first detected at 19 days of gestation (1197.0 ng/l), increased towards birth, and thereafter decreased (4588.5 +/- 572.3 ng/l at 21 days of gestation and 2400.0 +/- 179.6 ng/l at 5 days of age). These results indicate that Leydig cells in fetal and neonatal rats produce inhibin-related substances with no inhibin bioactivity, whereas Sertoli cells begin to produce inhibin during the perinatal period as a possible regulator of FSH secretion.

3-Hydroxysteroid Dehydrogenases↗

PubMed1999

Secretion of inhibin A, inhibin B and inhibin pro-alphaC during the oestrous cycle of the golden hamster (Mesocricetus auratus).

Plasma concentrations of inhibin pro-alphaC, inhibin A and inhibin B were determined by enzyme-linked immunosorbent assay at 6 h intervals throughout the 4-day oestrous cycle of the golden hamster. Plasma concentrations of follicle-stimulating hormone (FSH) and oestradiol-17beta were also measured by radioimmunoassay during the oestrous cycle. Plasma concentrations of inhibin A increased from the early morning of day 1 (day 1=day of ovulation) and reached plateau levels at 0500 h on day 2. An abrupt increase in plasma concentrations of inhibin A was found at 1700 h on day 4, when the preovulatory FSH surge was observed. An increase in plasma concentrations of inhibin B occurred on day 1 and reached plateau levels at 1700 h on day 1. The levels remained elevated until 0500 h on day 4 and declined gradually by 2300 h on day 4. Plasma concentrations of inhibin pro-alphaC gradually increased with some fluctuation from day 1 to 1700 h on day 4 and then declined. Significant negative relationships were noted between plasma FSH and both dimeric forms of inhibin from day 1 to day 3. Significant positive relationships were found between plasma oestradiol-17beta and inhibin A or inhibin pro-alphaC throughout the oestrous cycle. In contrast, no significant relationship was found between plasma oestradiol-17beta and inhibin B. These findings suggest that both dimeric forms of inhibin play a role in the regulation of FSH secretion during follicular development. These findings also suggest that inhibin pro-alphaC could be secreted primarily by large follicles, and early atretic follicles could also be responsible for inhibin pro-alphaC secretion. On the other hand, the secretory pattern of dimeric inhibins might shift from inhibin B to inhibin A with follicular development.

Animals↗

PubMed1988

The effect of hypophysectomy on inhibin production by adult rat ovaries: changes in ovarian inhibin gene expression and serum inhibin.

We have investigated the effect of hypophysectomy on adult rat ovarian inhibin alpha- and beta A-subunit mRNA, serum inhibin, and circulating gonadotrophin levels. Immediate declines in ovarian inhibin gene expression and serum inhibin were observed following hypophysectomy, with a nadir on day 4. However, inhibin synthesis determined by these parameters was still apparent at 16 days post-hypophysectomy. Gonadotropin levels were suppressed following hypophysectomy and the fall in inhibin production was highly correlated with disappearance of FSH from the circulation. This study demonstrates that removal of pituitary gonadotropin stimulation results in diminished ovarian inhibin synthesis and provides further evidence indicating that FSH stimulates granulosa cell inhibin synthesis by enhancing inhibin gene transcription.

Animals↗

PubMed1999

Inhibin A and inhibin B responses to gonadotropin withdrawal depends on stage of follicle development.

Previous studies demonstrate that inhibin A and B are differentially secreted across the menstrual cycle. To test the hypothesis that the responses of inhibin A and inhibin B to partial gonadotropin withdrawal are influenced by the stage of follicular development, a maximally suppressive dose of the Nal-Glu GnRH antagonist (150 microg/kg) was administered to normal cycling women during the midfollicular (MFP; n = 8), late follicular (LFP; n = 6), and midluteal phase (MLP; n = 5) to assess ovarian responsiveness over a broad range of developmental stages. Administration of the GnRH antagonist resulted in a significant decrease in LH (75 +/- 5%, 63 +/- 3%, and 84 +/- 7%; P < 0.05) and FSH (23 +/- 9%, 32 +/- 5%, and 39 +/- 6%; P < 0.04) during the MFP, LFP, and MLP, respectively. During the MFP, partial withdrawal of gonadotropins resulted in disappearance of the dominant follicle on ultrasound accompanied by a decrease in estradiol (E2; 64.9 +/- 11.4 to 23.9 +/- 3.3 pg/mL; P < 0.02) and inhibin B levels (121.6 +/- 14.8 to 28.4 +/- 4.8 pg/mL; P < 0.002) from baseline to near the limit of detection. Inhibin A was near the limit of detection in this cycle stage (0.8 +/- 0.1 IU/mL). When gonadotropins were withdrawn during the LFP, the size of the dominant follicle remained stationary in four of five subjects, and inhibin B (84.1 +/- 14.1 to 22.2 +/- 3.4 pg/mL; 71 +/- 5%; P < 0.02), inhibin A (4.4 +/- 1.1 to 1.3 +/- 0.5 IU/mL; 71 +/- 7%; P < 0.02), and E2 (236.8 +/- 48.2 to 95.6 +/- 39.0 pg/mL; 61 +/- 12%; P < 0.02) decreased similarly. Time to ovulation was shorter in association with higher inhibin A (r = -0.67; P < 0.02) and E2 (r = -0.79; P < 0.003), but there was no relation to inhibin B. During the MLP, decreased gonadotropin levels resulted in the disappearance of corpus luteum function with a significant decrease in inhibin A (9.0 +/- 0.4 to 0.7 +/- 0.1 IU/mL; 92 +/- 1%; P < 0.0001) in combination with decreased E2 (150.4 +/- 22.9 to 23.8 +/- 4.2 pg/mL; 83 +/- 3%; P < 0.005) and progesterone (12.6 +/- 2.6 to 0.9 +/- 0.2 ng/mL; 92 +/- 2%; P < 0.01). Administration of a GnRH antagonist at precise stages of the menstrual cycle provides further evidence that differential regulation of inhibin A and inhibin B is critically dependent on the stage of follicular development. Inhibin B secretion is exquisitely sensitive to gonadotropin withdrawal during the MFP when inhibin A has not yet risen. Inhibin A and inhibin B decrease equally after GnRH antagonist administration during the LFP. However, before antagonist administration, the positive correlation between estradiol and inhibin A and time to ovulation and the lack of such a correlation with inhibin B suggest that the source of inhibin B secretion is different from that of inhibin A and E2. The decrease in inhibin A secretion after antagonist administration during the luteal phase confirms gonadotropin-dependent secretion of dimeric inhibin A by the corpus luteum.

Adult↗

PubMed1995

Changes in inhibin-A (alpha-beta A dimer) and total alpha inhibin in the peripheral circulation and ovaries of rats after gonadotrophin-induced follicular development and during the normal oestrous cycle.

Recent modifications to a previously reported two-site IRMA have permitted the measurement of serum/plasma concentrations and ovarian contents of inhibin-A (alpha-beta A dimer) in pregnant mare serum gonadotrophin (PMSG)-treated immature female rats and adult rats throughout the 4-day oestrous cycle. For comparison, total alpha inhibin levels were also measured by alpha subunit-directed inhibin RIA and found to be at least tenfold higher (relative to the same 32 kDa bovine inhibin standard used to calibrate both assays). In immature female rats, serum levels of inhibin-A dimer and total alpha inhibin increased within 3 h of PMSG injection and rose in parallel over the next 48 h to values four- to fivefold higher than pretreatment levels. Ovariectomy led to a rapid and parallel fall in both inhibin-A dimer and total alpha inhibin; initial half-lives (+/- 95% confidence intervals) were 22 +/- 4 and 20 +/- 5 min respectively. In adult rats, marked fluctuations in plasma concentrations and ovarian contents of inhibin-A dimer and total alpha inhibin occurred during the 4-day oestrous cycle, most notably between the morning of pro-oestrus and the morning of oestrus. Plasma levels of inhibin-A dimer and total alpha inhibin peaked on the afternoon of pro-oestrus just before the preovulatory gonadotrophin surge. After ovulation, both inhibin-A dimer and total alpha inhibin fell abruptly (two- to threefold by 0200 h on oestrus; P < 0.001), while FSH showed a secondary rise which peaked at 0700 h on oestrus. Although IRMA- and RIA-derived inhibin values generally followed a similar pattern across the 4-day cycle (plasma: r = 0.52, P < 0.001; ovary: r = 0.41, P < 0.001), a transient rise in plasma and ovarian inhibin-A dimer was detected at 0700 h on oestrus (P < 0.01) which was unaccompanied by a rise in total alpha inhibin. This rise in plasma inhibin-A dimer was probably responsible for terminating the post-ovulatory FSH surge since FSH levels declined steadily over the next 15 h. Overall, plasma inhibin-A dimer and FSH concentrations across the whole cycle were negatively correlated (r = -0.22, P < 0.01) whereas no correlation existed between total alpha inhibin and FSH (r = -0.11, P = 0.12).

Animals↗

PubMed1998

Inhibin A, inhibin B and activin A concentrations in follicular fluid from women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by arrested follicle development at the early antral stage. Alterations in inhibin production by developing follicles could be involved in PCOS by suppressing follicle stimulating hormone concentrations during the follicular phase of the menstrual cycle as well as by increasing thecal androgen production. Inhibin B appears to be more important than inhibin A during the follicular phase; however, there are no data regarding the follicular fluid concentrations of inhibin B in PCOS. The purpose of this study was to compare inhibin A, inhibin B and activin A concentrations in the follicular fluid from regularly cycling women and women with PCOS. Inhibin A, inhibin B and activin A were measured in the follicular fluid of 4-7 mm follicles from PCOS ovaries and size-matched follicles from normally cycling women by specific and sensitive two-site enzyme-linked immunosorbent assays. In both control and polycystic ovaries, inhibin B was approximately 10-fold higher than activin A and more than 100-fold higher than inhibin A. There was no difference in activin A concentrations between PCOS and control follicles. In control ovaries, the inhibin B and inhibin A concentrations in dominant follicles were significantly higher than in cohort follicles. While inhibin A concentrations were lower in PCOS follicles than in normal cohort follicles, there was no difference in inhibin B concentrations between PCOS follicles and normal cohort follicles. These data are consistent with the concept that inhibin B is the physiologically most important form of inhibin during the follicular phase of the menstrual cycle and indicate that PCOS is not associated with increased inhibin B concentrations in follicular fluid.

Activins↗

PubMed1992

Testicular Leydig cells in vitro secrete only inhibin alpha-subunits, whereas Leydig cell tumors can secrete bioactive inhibin.

The secretion of inhibin and inhibin-related proteins by testicular Leydig cells was studied by estimation of inhibin immunoreactivity and bioactivity in spent media of preparations of immature and mature rat Leydig cells and of tumor Leydig cells. Immature and mature rat Leydig cells expressed inhibin alpha-subunit mRNA and secreted immunoreactive inhibin. The immunoreactive material did not contain inhibin bioactivity as measured by an in vitro rat pituitary bioassay system. Results of pulse labeling with [35S]methionine followed by immunoprecipitation indicated that the inhibin-related proteins secreted by the immature Leydig cell preparations are 26 kDa and 44 kDa molecules. Mature rat Leydig cells only secreted the 44 kDa inhibin-related protein. Tumor Leydig cells (rat H540 and mouse MA10) secreted immunoreactive and bioactive inhibin, which could be immunoneutralized by an antibody against inhibin. In the culture medium of some H540 tumor Leydig cells 26 kDa and 42 kDa inhibin-related proteins and 30 kDa inhibin were detected. In culture medium of other H540 tumor Leydig cells, not secreting bioactive inhibin, only 26 kDa and 42 kDa inhibin-related proteins were found. No activin bioactivity was detected in culture media of immature rat Leydig cells, H540 and MA10 tumor Leydig cells. It is concluded that normal Leydig cells secrete inhibin alpha-subunits, while Leydig cell tumors can also secrete bioactive inhibin. Neither normal Leydig cells nor Leydig cell tumors produce activin.

Activins↗

PubMed1999

Amniotic fluid levels of dimeric inhibins, pro-alpha C inhibin, activin A and follistatin in Down's syndrome.

OBJECTIVE: In the second trimester of pregnancy, inhibin A is significantly increased in maternal serum and decreased in amniotic fluid in Down's syndrome pregnancies compared to normal. We wished to further evaluate the levels of inhibin A, inhibin B, pro-alpha C inhibin, activin A and the binding protein follistatin in amniotic fluid in Down's syndrome and control pregnancies. DESIGN: Case-matched control study. PATIENTS: 29 Down's syndrome and 290 chromosomally normal control pregnancies were identified from records and amniotic fluid, collected at second trimester amniocentesis, retrieved from routine storage for analysis. MEASUREMENTS: Inhibin A, inhibin B, pro-alpha C inhibin, total activin A and follistatin were measured using sensitive and specific enzyme linked immunosorbent assays. RESULTS: The median (10th-90th percentiles) amniotic fluid inhibin A level in the control pregnancies increased from 334 (122-553) ng/l at 14 weeks' to 695 (316-1475) ng/l at 19 weeks' gestation. The corresponding figures for inhibin B and the alpha-subunit precursor inhibin pro-alpha C were 632 (185-1354) and 2062 (1237-3381) ng/l, respectively at 14 weeks' and 2439 (748-5307) and 3115 (2021-6567) ng/l, respectively at 19 weeks' gestation. Total activin A increased from 3795 (1554-5296) at 14 weeks' to 5086 (3059-8224) at 18 weeks' gestation. Expressed as multiples of the median (MoM) the median (95% CI) amniotic fluid levels of inhibin A, inhibin B, pro-alpha C inhibin and acitivin A in the Down's syndrome samples were 0.77 (0.59-0.85), 0.94 (0.63-1.23), 0.77 (0.49-0.84) and 0.77 (0.53-0.87), respectively. Compared to controls the levels of inhibin A, pro-alpha C inhibin and activin A were significantly lower in Down's syndrome pregnancies (P < 0.01, Mann-Whitney U test). Follistatin levels in the controls declined slightly from 2106 (1421-3538) ng/l at 14 weeks' to 1600 (1281-2543) ng/l at 18 weeks' gestation. Levels in the Downs' syndrome pregnancies were similar to controls. CONCLUSIONS: The data suggest that the production, secretion or metabolism of the inhibin alpha- and beta A-subunits is altered in Down's syndrome pregnancies in the second trimester.

Activins↗

PubMed1998

Identification of an inhibin receptor in gonadal tumors from inhibin alpha-subunit knockout mice.

Inhibins and activins are dimeric proteins that are functional antagonists and are structurally related to the transforming growth factor-beta (TGFbeta) family of growth and differentiation factors. Receptors for activin and TGFbeta have been identified as dimers of serine-threonine kinase subunits that regulate cytoplasmic proteins known as Smads. Despite major advances in our understanding of activin and TGFbeta receptors and signaling pathways, little is known about inhibin receptors or the mechanism by which this molecule provides a functionally antagonistic signal to activin. Studies described in this paper indicate that an independent inhibin receptor exists. Numerous tissues were examined for inhibin-specific binding sites, including the developing embryo, in which the spinal ganglion and trigeminal ganglion-bound iodinated inhibin A. Sex cord stromal tumors, derived from male and female inhibin alpha-subunit-deficient mice, were also identified as a source of inhibin receptor. Abundant inhibin and few activin binding sites were identified in tumor tissue sections by in situ ligand binding using iodinated recombinant human inhibin A and 125I-labeled recombinant human inhibin A. Tumor cell binding was specific for each ligand (competed by excess unlabeled homologous ligand and not competed by heterologous ligand). Based on these results and the relative abundance and homogeneity of tumor tissues versus the embryonic ganglion, tumor tissues were homogenized, membrane proteins were purified, and putative inhibin receptors were isolated using an inhibin affinity column. Four proteins were eluted from the column that bind iodinated inhibin but not iodinated activin. These data suggest that inhibin-specific membrane-associated proteins (receptors) exist.

Activin Receptors↗

PubMed1999

Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome.

To test the hypothesis that dimeric inhibin A and/or inhibin B concentrations represent improved markers of in-vitro fertilization (IVF) outcome over follicle stimulating hormone (FSH), 78 women who achieved pregnancy within three assisted reproduction treatment cycles were matched to 78 women who underwent at least three assisted reproductive treatment cycles and failed to achieve pregnancy. Baseline serum inhibin B and FSH were obtained between days 1 and 4 in a cycle prior to ovarian stimulation, and inhibin A and B were measured immediately before the ovulatory stimulus and in follicular fluid from the lead follicle. Comparing pregnant and non-pregnant subjects at baseline, younger age (34.0 +/- 0.5 versus 36.0 +/- 0.5 years; P < 0.003) and a combination of FSH lower than the median value (11.2 IU/l) and inhibin B higher than the median value (76.5 pg/ml) were associated with pregnancy (P < 0.03), but FSH (11.7 +/- 0.5 versus 12.9 +/- 0.9 IU/ml) and inhibin B (89.0 +/- 10.2 versus 79.7 +/- 7.7 pg/ml) were not independently associated. At the time of the ovulatory stimulus, serum inhibin A (52.8 +/- 3.8 versus 40.0 +/- 2.7 IU/ml; P < 0.004), inhibin B (1623.8 +/- 165.1 versus 859.2 +/- 94.8 pg/ml; P < 0.0009) and the number of oocytes retrieved (14.6 +/- 0.8 versus 10.1 +/- 0.6; P < 0.0001) were predictive of pregnancy when controlled for age. Inhibin A was correlated with the number of embryos (r = 0.4; P < 0.0001). However, neither inhibin A nor inhibin B provided additional information in predicting successful outcome over age and number of oocytes. We conclude that: (i) in patients undergoing assisted reproductive technology, age and number of oocytes retrieved are the strongest predictors of success; (ii) of the parameters available prior to cycle initiation, a combination of lower FSH and higher inhibin B was associated with a greater chance for a successful outcome but an absolute cut-off could not be defined; and (iii) during ovarian stimulation, higher concentrations of inhibin A and inhibin B in serum are associated with successful IVF and mark ovarian reserve as a measure of oocyte number and quality.

Adult↗

PubMed1999

Activin A, inhibin A, inhibin B and parturition: changes of maternal and cord serum levels according to the mode of delivery.

OBJECTIVE: To evaluate whether activin A, inhibin A, and inhibin B levels in maternal and umbilical artery serum change according to the mode of delivery. DESIGN: Maternal and cord blood specimens were collected at term after spontaneous labour and vaginal delivery, or elective caesarean section. SETTING: Universities of Pisa, Turin, Naples and Udine. POPULATION: Forty-two healthy pregnant women, at 3940 weeks of gestation, divided into two subgroups: group 1 vaginal delivery (n = 21), were delivered of 10 female and 11 male infants; group 2 elective caesarean section (n = 21), were delivered of 11 female and 10 male infants. MAIN OUTCOME MEASURES: Serum activin A, inhibin A, inhibin B concentrations in maternal and umbilical cord blood. RESULTS: At vaginal delivery, maternal serum inhibin A and inhibin B levels were lower and activin A levels higher than at elective caesarean section. Maternal levels of activin A, inhibin A and inhibin B were constantly higher than in umbilical arterial blood, independent of the mode of delivery. No significant difference was observed in umbilical arterial serum levels of the three proteins between the two modes of delivery. Umbilical arterial serum activin A and inhibin A concentrations did not show a significant difference between male and female infants in either vaginal or caesarean section, but male infants showed inhibin B levels significantly higher than female, independent of the mode of delivery. CONCLUSIONS: In the presence of active labour, the human placenta secretes larger amounts of activin A and lesser amounts of inhibin A and inhibin B into the maternal circulation. Inhibin-related proteins in the fetal circulation do not show differences according to the mode of delivery, suggesting that they have a different method of production or metabolic rate compared with maternal activin and inhibins.

Activins↗

PubMed1999

A selective increase in circulating inhibin and inhibin pro-alphaC at the time of ovulation in the mare.

The relationship between a selective increase in circulating immunoreactive (ir)-inhibin and the time of ovulation was investigated in mares. Concentrations of plasma ir-inhibin were measured every 4 h during the periovulatory period. Inhibin pro-alphaC, a precursor protein of the inhibin alpha-subunit, was also measured. The changes in ir-inhibin and inhibin pro-alphaC in circulation were parallel. Concentrations of both ir-inhibin and inhibin pro-alphaC in the plasma increased at the same time when ovulatory follicles ruptured, and the peak levels of circulating ir-inhibin and inhibin pro-alphaC were maintained for 4-8 h. There was no selective increase in plasma concentrations of estradiol-17beta during the process of ovulation. These results suggest that the selective increase in ir-inhibin and inhibin pro-alphaC was caused by the absorption of follicular fluid after the rupture of ovulatory follicles. These results also suggest that the measuring of plasma concentrations of ir-inhibin or inhibin pro-alphaC in mares might be a useful method for detecting the time of ovulation.

Animals↗

PubMed1986

Measurement of exogenous and endogenous inhibin in sheep serum using a new and extremely sensitive bioassay for inhibin based on inhibition of ovine pituitary FSH secretion in vitro.

An extremely sensitive and reliable bioassay for inhibin based on inhibition of ovine pituitary FSH secretion in vitro was developed and used to measure exogenous and endogenous inhibin activity in the ewe. The sheep inhibin bioassay is 30- to 40-fold more sensitive than conventional rat inhibin bioassays. The minimum sensitivity of each bioassay in the measurement of inhibin activity in 1 ml of sheep serum is 220 mu. and 4080 mu. in the sheep and rat bioassays respectively. This sensitive inhibin bioassay has permitted, for the first time, the measurement of endogenous inhibin in the peripheral and ovarian vein blood of the sheep, as well as exogenously administered inhibin. The half-life of exogenously administered ovine inhibin (in follicular fluid) in the sheep was calculated as two components (18-24 and 50-60 min) from the inhibin profiles of six ewes. Inhibin contained in the ovine follicular fluid, given as a bolus i.v. injection, increased to maximum levels after 5 min and then remained increased for 10-32 min depending upon the dose administered, before exponentially decaying. The time for inhibin to exert its effect ranged from 3 to 6 h after injection and appeared to be dose-related. The bolus injection of inhibin, apart from causing suppression of FSH, evoked a large rebound increase of FSH up to 400% of preinjection levels. The development of the sheep bioassay will allow the measurement of biologically active inhibin in the peripheral circulation and ovarian vein blood of sheep with the possibility of extending this to man.

Animals↗

PubMed1997

Production of inhibin A and inhibin B in human ovarian sex cord stromal tumors.

OBJECTIVE: Our purpose was to examine the cellular localization of inhibin subunits and messenger ribonucleic acid expressions for the inhibin subunits and the serum levels of inhibin A and inhibin B in human ovarian sex cord stromal tumors. STUDY DESIGN: We examined the immunohistochemical localization of the inhibin subunits and the expression of the corresponding messenger ribonucleic acids by Northern blot analysis in a granulosa cell tumor and a Sertoli-Leydig cell tumor. We also measured serum concentrations of dimeric inhibin A and inhibin B by two-site enzyme-linked immunosorbent assay. RESULTS: Immunostaining specific for the inhibin alpha, betaA, and betaB subunits was observed in the granulosa cell tumor. In the Sertoli-Leydig cell tumor we observed immunostaining specific for the alpha subunit in Leydig tumor cells and that specific for the betaA subunit in Sertoli tumor cells and that specific for the betaB subunit in both tumor cells. Northern blot analysis revealed the presence of messenger ribonucleic acids for the alpha, betaA, and betaB subunits in the granulosa cell tumor and the Sertoli-Leydig cell tumor. The serum levels of dimeric inhibin A and inhibin B in patients were elevated preoperatively and decreased progressively after surgery. CONCLUSION: Our results suggest that inhibin A and inhibin B are produced by the human sex cord stromal tumors and that inhibins might be the useful markers of the tumors.

Adolescent↗

PubMed1996

Unique recognition of activin and inhibin by polyclonal antibodies to inhibin subunits.

Inhibin-A is a glycoprotein composed of an alpha subunit containing a glycosylation site and a beta A subunit, whereas activin-A is a homodimer of two inhibin beta A subunits. We examined the recognition of activin-A and inhibin-A by several antisera to the alpha or beta A subunit, and factors affecting the recognition. A total of six polyclonal antibodies to inhibin subunits, i.e., two antisera to a peptide fragment of the alpha subunit [alpha (1-19) and alpha (1-26)], and four antisera to the beta A subunit [beta A (1-10), beta A (70-79), beta A (87-99), and beta A (94-105)], was generated. On Western blot analysis, the anti-beta A (87-99) and beta A (94-105) sera recognized recombinant human activin-A but not inhibin-A under non-reducing conditions. When inhibin-A was deglycosylated with N-glycosidase-F, inhibin-A could be recognized by the anti-beta A (87-99) and beta A (94-105) sera. In addition, when activin-A bound to a nitrocellulose membrane was pre-incubated with recombinant human follistatin, the recognition of activin-A by the anti- beta A (87-99) and beta A (94-105) sera was decreased. These results suggested that the lower affinity of follistatin to inhibin-A than to activin-A might be likely explained as reflecting a site associated with the glycosylation of inhibin-A. However, the exposure of amino acids 87-105 of the inhibin beta A subunit on the molecular surface through deglycosylation did not increase the affinity of inhibin-A for follistatin but rather resulted in poor binding with follistatin. The present data suggest that (1) amino acids 87-105 of the inhibin/activin beta A subunit are located on the molecular surface, although this region of inhibin-A is concealed by the carbohydrate chain of the alpha subunit, (2) the region responsible for follistatin binding within the activin beta A subunit is spanned by amino acids 87-105, and (3) the mode of binding of inhibin-A to follistatin is quite different from that of activin-A to follistatin, and the former may be influenced by glycosylation.

Activins↗

PubMed1986

Measurement of inhibin and an index of inhibin production by rat testes during postnatal development.

Our previous studies have shown that inhibin activity in rat testes can be measured using an in vitro inhibin bioassay. In animals that have undergone unilateral efferent duct ligation (EDL), the difference in inhibin content between the ligated and nonligated testis can be used as an index of the rate of inhibin production in vivo. In the present study we examined postnatal changes in inhibin content in the testes, and the production rates of inhibin and seminiferous tubule fluid in groups of neonatal, immature, and adult rats from 1 to 80 days old. We detected inhibin activity in testes of 1-day-old rats; the activity level rose linearly to Day 8, subsequently increasing markedly from Day 30 until it reached a plateau at Day 45. Increments in the content of inhibin and weight of the testis after unilateral EDL, interpreted to represent production of inhibin and seminiferous tubule fluid, commenced at Day 20 and increased rapidly between Days 30 and 50, decreasing thereafter to Day 80. The increase in content and production of inhibin was directly correlated to the rise in serum follicle-stimulating hormone (FSH) and testosterone, suggesting that these two hormones are important in controlling inhibin secretion. In addition, the changes in serum FSH from the high, postnatal levels to those typical of adults were inversely correlated to the content and production rate inhibin in the testes and concentrations of testosterone in the serum. These data support the hypothesis that inhibin is specifically involved in the feedback control of pituitary FSH secretion during postnatal development, although a role for testosterone or a synergistic interaction between the two hormones cannot be excluded.

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