Plasma Levels Of Inhibin Research Articles

Testicular Toxicity of Water Pipe Smoke Exposure in Mice and the Effect of Treatment with Nootkatone Thereon

There is a worldwide increase in the popularity of water pipe (shisha) tobacco smoking including in Europe and North America. However, little is known about the effects of water pipe smoke (WPS) exposure on male reproductivity. We have recently demonstrated that WPS exposure in mice induces testicular toxicity including inflammation and oxidative stress. Nootkatone, a sesquiterpenoid found in grapefruit, has antioxidant and anti-inflammatory effects. However, the possible protective effect of nootkatone on WPS-induced testicular toxicity has not been reported before. Here, we tested the effects of treatment of mice with nootkatone on WPS-induced testicular toxicity. Mice were exposed to normal air or WPS (30 minutes/day, for 30 days). Nootkatone (90 mg/kg) was given orally to mice by gavage, 1 h before WPS or air exposure. Nootkatone treatment significantly ameliorated the WPS-induced increase in plasma levels of inhibin, uric acid, and lactate dehydrogenase activity. Nootkatone also significantly mitigated the decrease in testosterone, androgen-binding protein, and estradiol concentrations in the plasma induced by WPS. In testicular homogenates, WPS exposure caused a decrease in the total nitric oxide level and an increase in the proinflammatory cytokine interleukin-1β level and oxidative stress markers including malondialdehyde, cytochrome C, and 8-Oxo-2′-deoxyguanosine. All the latter effects were significantly alleviated by nootkatone treatment. Moreover, in testicular homogenate, nootkatone inhibited the expression of nuclear factor-kappaB induced by WPS. Likewise, histological examination of mouse testes showed that nootkatone treatment ameliorated the deterioration of spermatogenesis induced by WPS exposure. We conclude that nootkatone ameliorated the WPS-induced testicular inflammation and oxidative stress and hormonal and spermatogenesis alterations.

Inhibin B and Antimüllerian Hormone as Markers of Gonadal Function after Treatment for Medulloblastoma or Posterior Fossa Ependymoma during Childhood

To evaluate the roles of hypothalamic-pituitary and spinal irradiations and chemotherapy in gonadal deficiency after treatment for medulloblastoma or posterior fossa ependymoma by measuring levels of plasma inhibin B and antimüllerian hormone (AMH). A total of 34 boys and 22 girls were classified as having normal levels of plasma follicle-stimulating hormone (FSH; <9 IU/L), or abnormal levels of FSH (>9 IU/L) and luteinizing hormone (LH; <5 or >5 IUL). Two boys had partial gonadotropin deficiency, combined with testicular deficiency in one boy. Six boys had increased levels of FSH, indicating tubular deficiency, combined with Leydig cell deficiency in 5 boys. The 7 boys with inhibin B levels <100 ng/mL included the one with combined deficiencies and the 6 with testicular deficiency. Puberty did not progress in 7 girls; 3 had gonadotropin deficiency, combined with ovarian deficiency in one, and 4 had increased FSH levels, indicating ovarian deficiency. Inhibin B and AMH levels were low in the girl with combined deficiencies, in the 4 girls with ovarian deficiency, and in 4 girls with normal clinical-biological ovarian function, including 2 who underwent ovarian transposition before irradiation. The plasma concentrations of inhibin B and AMH are useful means of detecting primary gonad deficiency in patients with no increase in their plasma gonadotropin levels because of radiation-induced gonadotropin deficiency.

ALTERATIONS IN CONCENTRATIONS OF INHIBIN IN RELATION TO FSH AND STEROIDS HORMONE DURING ESTROUS CYCLE IN EGYPTIAN BUFFALOES

Seven Egyptian buffaloes were used to study the plasma changes of inhibin, FSH, estradiol-17b and progesterone concentrations during the at estrous cycle. These hormones were determined at estrous and two interval until day twenty two of estrous cycle. Plasma inhibin estimated by enzyme-linked immunoasorbent assay (ELISA). Both FSH, estradiol-17β and progesterone were estimated by radioimmunoassay (RIA). In order to elucidiate the feedback system controlling mentioned hormones during estrous cycle, variations in the levels of hormones and their inter-relationshpis were studied. Plasma inhibin levels ranged between 439.28 and 584 pg/ml during various stages of estrous cycle, peak of inhibin level was at day of estrous by an average of 584 pg/ml. Follicle stimulating hormone levels were higher at day of estrous (25.48 ng/ml), decreased and fluctuated towards end of estrous cycle and then increased at twenty two days of estrous cycle. Peak of estradiol-17β was 18.54 pg/ml at day of estrous, while the peak of progesterone was 4.39 ng/ml at twelfth day from the start of estrous. It could be concluded that each of inhibin and estradiol-17b seems to have a feedback regulatory effect on FSH secretion in buffaloes. Key words: Inhibin, FSH, estradiol-17b, progesterone, estrous cycle, buffalo.

Suppression of the high endogenous levels of plasma FSH in infertile men are associated with improved Sertoli cell function as reflected by elevated levels of plasma inhibin B

In vitro continuous stimulation of Sertoli cells with FSH leads to a desensitization of these cells to FSH action. To evaluate the presence of a desensitization of FSH receptor on Sertoli cells in vivo, we performed a controlled clinical study in 97 men affected by severe oligozoospermia. On the basis of FSH and inhibin B plasma concentrations, these subjects were divided into three groups: group A, 33 subjects with high FSH and low inhibin B plasma levels; group B, 32 subjects with high FSH plasma levels and inhibin B concentrations at the lower limit of the normal range; and group C, 32 subjects with normal FSH and inhibin B plasma levels. Patients with high FSH plasma levels (groups A and B) were prospectively randomized into two subgroups, called A1, A2, B1 and B2. Patients of groups A1 and B1 were treated with a GnRH agonist, leuprolide acetate, to induce a hypogonadotrophic state and then were treated with recombinant human FSH (r-hFSH; 100 IU/day) and hCG (2000 IU/twice a week) for 2 months. Subjects of groups A2, B2 and C were treated only with r-hFSH for the same period. In patients of group A1, inhibin B remained unmodified during the whole period of study, whereas in subjects of group B1, we observed a significant reduction of this hormone during the hypogonadotrophic period and then an increase of inhibin B plasma levels that were higher that those observed before therapy. In patients of groups A2 and B2, FSH treatment did not induce a significant increase in inhibin B concentrations. In patients of group C, FSH induced a significant increase in inhibin B plasma levels. In infertile men, suppression of the high endogenous levels of plasma FSH associated with much lower exogenous FSH levels is able to evoke higher inhibin B production, which may indicate improved Sertoli cell function and the possibility that this could have a positive effect on spermatogenesis.

Changes in circulating concentrations of inhibins A and pro-alpha C during first trimester medical termination of pregnancy.

Both inhibin A and inhibin pro-alpha C are detectable in the circulation in increasing amounts during establishment of pregnancy. However, their origins and functions remain to be elucidated. We have studied levels of inhibin A and inhibin pro-alpha C in serum samples collected at various stages during medical termination of pregnancy with consecutive use of mifepristone and misoprostol. Samples were collected from three groups of patients at different weeks of gestation (group A: 6-7 weeks, n = 6; group B: 7-8 weeks, n = 6; group C: 8-9 weeks, n = 6) at the time of administration of oral mifepristone, 48 h later just before administration of vaginal misoprostol and again soon after expulsion of the products of conception. Plasma concentrations of inhibin A and pro-alpha C were assayed using specific and sensitive enzyme-linked immunosorbent assays. Results were correlated with concentrations of hCG and progesterone. We observed a significant fall in plasma concentration of inhibin pro-alpha C following administration of mifepristone, which continued after administration of misoprostol. In contrast mifepristone had no effect on plasma levels of inhibin A, which fell steeply only after administration of misoprostol. These results suggest dissociation between major sources of inhibin A and inhibin pro-alpha C in early pregnancy. Treatment with mifepristone, a competitive antagonist of the progesterone receptor, resulted in a significant and rapid fall in concentrations of inhibin pro-alpha C, identifying a link between production of pro-alpha C and luteal steroidogenesis. In contrast, concentrations of inhibin A did not fall after mifepristone, identifying a predominantly feto-placental origin in early human pregnancy.

Effect of embryonic 19-nortestosterone treatment and surgical bursectomy on plasma concentrations of reproductive hormones, on inhibin content in adrenals and gonads and on the histological appearance of the gonads in the young chicken

Four-day-old chick embryos were hormonally treated with 19-nortestosterone in order to inhibit bursa development. At days 1, 4, 8, 15, 22, 29, and 36 of age, plasma, adrenals, and gonads from intact and hormonal treated chicks were collected. In embryonic nortestosterone treated males the appearance of a left ‘ ovotestis-like’ gonad was observed. The occurrence of this ovotestis-like left gonad in the 19-nortestosterone treated male is probably a secondary effect of the in ovo treatment since surgically bursectomised chicks did not show the testicular morphology and histological changes as observed in 19-nortestosterone treated chicks. Additionally, both male and female hormonally or surgically treated chicks showed relatively enlarged adrenal glands. Hormonal bursectomy affected organ inhibin contents and plasma inhibin, testosterone, and FSH levels in males. Male hormonal treated chicks showed lower levels of plasma inhibin ( p=0.0001), testosterone ( p=0.01), and FSH ( p=0.004), and a lower total testes inhibin content ( p=0.0003) compared to intact chicks. However, none of these were significantly different between female intact and hormonal treated chicks, again indicating that the observed hormonal changes in males are not the result of the disappearance of the bursa but of the hormonal 19-NT treatment. The total adrenal inhibin content as well as the adrenal inhibin concentration were significantly higher in hormonally treated chicks than in intact chicks ( p=0.0001), regardless of the sex.

Regulation of follicle-stimulating hormone secretion by estradiol and dimeric inhibins in the infantile female rat.

Plasma and ovarian levels of the dimeric forms of inhibin and plasma estradiol-17beta were investigated and compared with changes in plasma gonadotropins from Postnatal Day (PND) 5 to PND 30 in the female rat. The inhibin subunit proteins were localized in follicular granulosa cells of the ovary. Plasma immunoreactive inhibin levels were low until PND 15 and increased thereafter. Plasma levels of inhibin B (alpha and beta(B) subunits) remained very low until PND 15 and then increased by approximately 24-fold. In contrast, plasma levels of inhibin A (alpha and beta(A) subunits) were relatively low and steady until PND 20, then increased by approximately 3-fold at PND 25. Changes in ovarian inhibin A and B levels closely resembled those in plasma levels. Plasma FSH levels were low at PND 10 but started to peak from PND 15 and remained high until PND 20, followed by a remarkable reduction at PNDs 25 and 30. This dramatic fall in FSH coincided with the rise of inhibin A. A significant inverse correlation was observed between plasma FSH and plasma inhibin A (r = -0.67, P < 0.0002), ovarian inhibin A (r = -0.48, P < 0.01), plasma inhibin B (r = -0.48, P < 0.05), and ovarian inhibin B (r = -0.54, P < 0.01). Plasma estradiol-17beta levels were elevated from PND 5 through PND 15, then fell sharply through PND 30. Plasma estradiol-17beta was significantly and positively (r = 0.75, P < 0.0002) correlated with plasma FSH. Plasma LH rose to higher levels at PND 15 and tended to be lower thereafter. The inhibin alpha, beta(A), and beta(B) subunits were localized to primary, secondary, and antral and large antral follicles, but the types of these immunopositive follicles varied with age. It appeared that, at PND 25 and afterward, all three subunits were mainly confined to large antral follicles in the ovary. We conclude that estradiol-17beta likely is the major candidate in stimulation of FSH secretion in the infantile female rat. We also conclude that inhibin regulation of pituitary FSH secretion through its negative feedback in the infantile female rat begins to operate after PND 20. We suggest that this negative feedback is achieved by increases in plasma levels of the two dimeric forms, and that inhibin A appears to be the major physiological regulator of FSH secretion at the initiation of this mechanism. We also conclude that large antral follicles in the ovary are the primary source of these bioactive inhibins that are secreted in large amounts into the circulation after PND 20.

Plasma Inhibin Levels in Relation to Steroids and Gonadotrophins during Oestrous Cycle in Buffalo

The study was conducted on six Murrah buffalo synchronized and induced to oestrus. An indwelling catheter was placed in the jugular vein of each buffalo 4 days before the expected onset of the oestrus following the induced oestrus and blood samples were collected at 8 h intervals from each animal throughout the oestrous cycle. Plasma immunoreactive inhibin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol-17 beta and progesterone were estimated by radioimmunoassay to study the variations in the peripheral levels of these hormones and their inter-relationships in order to elucidate the feedback systems controlling them during the oestrous cycle of buffalo. Plasma inhibin levels ranged between 391.25 and 631.97 pg/ml during various phases of the oestrous cycle and were found to be higher than reported in cows. Peak LH and FSH levels during oestrus were 38.40 +/- 9.21 and 24.04 +/- 4.75 ng/ml, respectively and estradiol-17 beta and progesterone were 19.50 +/- 5.51 pg/ml and 0.61 +/- 0.25 ng/ml, respectively. The mean plasma inhibin concentration on the day of oestrus was 562.5 +/- 18.9 pg/ml. Levels of FSH in the plasma showed three mid-cycle elevations which corresponded to comparatively lower inhibin and elevated estradiol-17 beta levels during the same period. From this observation it was deduced that both inhibin and estradiol-17 beta have a feed-back regulatory effect on FSH secretion in buffalo.

Changes in plasma inhibin A levels during sexual maturation in the female chicken and the effects of active immunization against inhibin alpha-subunit on reproductive hormone profiles and ovarian function.

Inhibins and activins are firmly implicated in the control of pituitary FSH secretion and ovarian follicular development in mammals. As in mammals, inhibin A and activin A are expressed in the preovulatory follicles of birds, and a defined ovulation cycle for inhibin A has recently been demonstrated in the laying hen. To investigate further the role of inhibin-related proteins in developing pullets, circulating concentrations of inhibin A, inhibin B, total immunoreactive inhibin alpha-subunit (ir-alpha), activin A, LH, FSH, and progesterone were measured from the juvenile state through to sexual maturity in 22 birds. In the 11 birds assigned to control groups, plasma inhibin A levels were low from 7 to 13 wk of age rising about threefold to a peak at Week 19 after which levels fell slightly to a plateau level characteristic of adult hens. Plasma inhibin A levels were negatively correlated with FSH (r = -0. 33; P: < 0.001) and positively correlated with progesterone (r = 0. 67; P: < 0.001) and ir-alpha (r = 0.53; P: < 0.001). Plasma ir-alpha levels were much higher than inhibin A levels although the relative differences varied with age. Plasma levels of inhibin B and activin A were below assay detection limits at all times. The remaining group of 11 birds was actively immunized (IMM) against a synthetic chicken inhibin alpha-subunit peptide (amino acids 1-26). The IMM generated circulating antibodies that bound native bovine inhibin A but altered neither plasma FSH nor progesterone levels relative to control birds at any stage of development nor the timing of first oviposition in week 19. Apart from a transient decline 1 wk after primary IMM, plasma LH concentrations did not differ from controls. Comparison of the numbers and size-class distribution of ovarian follicles at 29 wk showed an approximate twofold increase in the number of 8- to 9.9-mm-diameter follicles (control; 1.82 +/- 0.44 vs. IMM; 3.91 +/- 0.89; P: < 0.05), a size class that corresponds to follicles that have just joined the preovulatory hierarchy. The numbers of growing follicles in other size-classes and the sizes of hierarchical F(1)-F(7) follicles were not altered by IMM. However, the number of postovulatory follicles increased (control 3.73 +/- 0. 20 vs. IMM 5.55 +/- 0.28; P: < 0.01), and significantly more (P: < 0. 02) immunized hens laid two eggs within a 24-h period on at least one occasion (control 1 of 11 vs. IMM 9 of 11). The IMM increased (P: < 0.05) activin A content of F(1) and F(2) theca layers and decreased (P: < 0.05) activin A content in F(3) and F(4) granulosa layers, raising the possibility of a local intraovarian role of activin in mediating the response to IMM. These findings support a role for inhibin A in regulating the entry of follicles into the preovulatory hierarchy in the chicken, although further studies are required to establish the mechanism by which inhibin IMM increases the rate of follicle selection and ovulation without raising plasma FSH.

Changes in Plasma Levels of Inhibin and Follicle Stimulating Hormone in Buffaloes Superovulated with eCG

Changes in Plasma Levels of Inhibin and Follicle Stimulating Hormone in Buffaloes Superovulated with eCG

Involvement of inhibin in the regulation of follicle-stimulating hormone secretion in the young adult male Shiba goat.

The roles of inhibin and testosterone in the regulation of gonadotropin secretion were investigated in young adult male Shiba goats (8-12 months of age). Plasma levels of inhibin but not testosterone abruptly decreased after hemicastration (75% of the initial level), concomitant with a progressive rise in plasma levels of FSH. Removal of the remaining testis at 33 days after the hemicastration quickly decreased plasma levels of both inhibin and testosterone and induced a progressive increase in plasma FSH and LH. Implantation of testosterone sheets immediately after castration suppressed the increase in plasma FSH in part only, whereas the increase in LH secretion was almost completely suppressed. An i.v. injection of antiserum against [Tyr30] porcine inhibin alpha(1-30) resulted in a significant increase in plasma FSH in a dose-dependent manner, without altering plasma concentrations of LH. These findings clearly indicate that both inhibin and testosterone physiologically regulate FSH secretion and that testosterone is the principal gonadal factor regulating LH secretion in the adult male goat.

Inhibin B levels in plasma of the male rat from birth to adulthood: effect of experimental manipulation of Sertoli cell number.

Sertoli cells undergo important changes in their number and function at different ages in the rat and may be the primary source of circulating inhibin B. The aims of this study were 1) to establish the profile of inhibin B levels from birth to adulthood in normal rats and 2) to identify whether experimental manipulation of Sertoli cell numbers was able to alter this profile. Levels of inhibin B, measured by a specific two-site assay, increased fivefold in normal Wistar rats between day 3 and days 10-15, plateaued, and then declined in late puberty to reach adult levels which were approximately 60% of those observed on days 10-15. The increase in inhibin B levels in the neonatal period coincided with the period of Sertoli cell multiplication as indicated by incorporation of bromodeoxyuridine. Neonatal treatment of rats with a GnRH antagonist (GnRHa) reduced Sertoli cell number and adult testis weight by 48% and significantly reduced plasma levels of inhibin B at all ages through to adulthood. Induction of neonatal hypothyroidism in Sprague-Dawley rats by administration of propylthiouracil (PTU) up to day 25 of age increased final testis weight by 41% (indicative of increased Sertoli cell numbers) and resulted in elevation of plasma levels of inhibin B at all ages beyond 7 days of age. The degree of change in inhibin B levels in adult rats in the two experimental treatment groups was approximately proportional to the change in final testis weight. Plasma follicle-stimulating hormone (FSH) showed changes opposite to inhibin B, with levels being lowered in PTU-treated rats and elevated (beyond day 25) in GnRHa-treated animals. The present results suggest that final Sertoli cell number per testis exerts an important effect on the circulating level of inhibin B (and FSH) in the rat. These findings are compared to the emerging data for the human male.

Changes in plasma levels of inhibin and follicle stimulating hormone in buffaloes superovulated with PMSG

Changes in plasma levels of inhibin and follicle stimulating hormone in buffaloes superovulated with PMSG

Circadian and pulsatile variations in plasma levels of inhibin, FSH, LH and testosterone in adult murrah buffalo bulls

The present study investigated pulsatile and circadian variations in the circulatory levels of inhibin, gonadotrophins and testosterone. Six adult buffalo bulls (6 to7 yr of age) were fitted with indwelling jugular vein catheters, and blood samples were collected at 2-h intervals for a period of 24 h and then at 15-min interval for 5 h. Plasma concentrations of inhibin, FSH, LH and testosterone were determined by specific radioimmunoassays. Plasma inhibin levels in Murrah buffalo bulls ranged between 0.201 to 0.429 ng/mL, with a mean of 0.278±0.023 ng/mL. No inhibin pulses could be detected during the 15-min sampling interval. Plasma FSH levels ranged between 0.95 to 3.61 ng/mL, the mean concentration of FSH over 24 h was 1.66±0.25 ng/mL. A single FSH pulse was detected in 2 of 6 bulls. The LH levels in peripheral circulation ranged between 0.92 to 9.91 ng/mL, with a mean concentration of 3.33±1.02 ng/mL. Pulsatility was detected in LH secretion with an average of 0.6 pulses/h. Plasma testosterone levels in 4 buffalo bulls ranged from 0.19 to 2.99 ng/ mL, the mean level over 24 h were 1.34±0.52 ng/mL. Testosterone levels in peripheral circulation followed the LH secretory pattern, with an average of 0.32 pulses/h. The results indicate parallelism in inhibin, FSH and LH, and testosterone secretory pattern. Divergence in LH and FSH secretory patterns in adult buffalo bulls might be due to the presence of appreciable amounts of peripheral inhibin.

Peripheral inhibin levels in relation to climatic variations and stage of estrous cycle in buffalo ( [formula omitted

The present study investigated the peripheral plasma inhibin levels in relation to 1) the stage of estrous cycle and the effect of climatic variations. Blood samples were collected from cyclic buffalo (n=5) once daily for 32 consecutive days during the tropical hot humid (summer) and cold (winter) seasons. Estrus was recorded by parading a vasectomized bull as well as by plasma progesterone determination. In the winter season, peripheral inhibin concentrations which were lowest (0.35 ± 0.02 ng/ml) during the mid-luteal phase of estrous cycle (Day 6 to Day 14, Day 0 = day of estrus) increased significantly (P < 0.02) to 0.47 ± 0.04 ng/ml during the late luteal phase (Day −4 to Day −2) and then further to 0.52 ± 0.03 ng/ml (P< 0.02) during the periestrus phase (Day −1 to Day 1). Inhibin concentrations then decreased significantly (P < 0.02) to 0.40 ± 0.03 ng/ml during the early luteal phase (Day 2 to Day 5). In the summer season the differences in peripheral inhibin concentrations among different phases of estrous cycle were found to be nonsignificant. A comparison of the circulating inhibin concentrations between the two seasons indicated that inhibin concentrations were significantly higher in the late luteal phase (P < 0.01) and periestrus phase (P < 0.05) during the winter season compared with corresponding periods during the summer season. The present study suggests that peripheral inhibin concentrations change in the estrous cycle during cooler breeding season and that environmental heat stress can cause a reduction in peripheral inhibin concentrations.

Temporal Changes in Inhibin, Steroid Hormones, and Steroidogenic Enzymes during Induced Follicular Atresia in the Hypophysectomized Cyclic Hamster1

The time course for loss of ability of Graafian follicles to secrete inhibin and estradiol was investigated during induced follicular atresia. Cyclic hamsters were hypophysectomized on Day 1 (estrus) and injected s.c. with 30 IU eCG. Thereafter, these animals were given a single i.p. injection of antiserum to eCG on the morning of Day 4 to induce follicular atresia in a rapid and predictable manner. A drastic fall in plasma levels of estradiol and testosterone was noted within 1 h, whereas relatively high levels of plasma inhibin were maintained until 12 h, followed by an abrupt decline by 24 h. The first histological signs of pyknosis in granulosa cells appeared by 4 h, and breakdown of the mural granulosa layer was observed in most follicles by 8-12 h after immunoneutralization of circulating eCG. According to immunohistochemical analysis, inhibin activity was unchanged in granulosa cells at 12 h followed by a slight decline by 24 h, whereas positive reaction for aromatase in these cells rapidly declined by 8 h. Immunoreactivity of 17alpha-hydroxylase/C17,20-lyase (CYP 17) was also reduced in theca cells by 8 h. These results indicate that granulosa cells continue to secrete inhibin during the process of follicular atresia, although these cells quickly shut off the secretion of estradiol, and theca cells shut off the secretion of testosterone. The present results indicate as well that a rapid decline of estradiol and testosterone in plasma is an early sign of atresia in antral follicles. These results, therefore, suggest that the loss of enzymatic activity of aromatase in granulosa cells and CYP 17 in theca cells is a part of the process of follicular atresia.

Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

Effects of continuous inhibin administration on gonadotropin secretion and subunit gene expression in immature and adult male rats.

To begin to examine inhibin as a male contraceptive, recombinant human (rh) inhibin-A was administered for 3 days via osmotic minipumps to male rats. Doses of inhibin of 0-150 mg/kg per day did not produce a concentration-dependent suppression of FSH secretion or pituitary FSH beta mRNA levels in adult rats. Treatment of immature rats at a dose of 145 micrograms/kg per day, which was without effect in adults, reduced plasma FSH levels by 49% (p < 0.01), and FSH beta mRNA levels to 47 +/- 11% of control (p < 0.01). Inhibin also decreased levels of LH beta mRNA (63 +/- 8% of control; p < 0.01), alpha-subunit mRNA (86 +/- 10% of control; p < 0.05), and GnRH-receptor mRNA (77 +/- 17% of control; p <0.01) in immature rats. Rh inhibin-A was more effective in immature than in adult animals; plasma inhibin levels were increased (p = 0.03) by rh inhibin-A treatment only in immature rats. Pharmacokinetic studies revealed that the weight-adjusted clearance was greater (p < 0.01), and the elimination half-life of rh inhibin A was shorter (p < 0.01) in adult than in juvenile rats. These data indicate that partial suppression of FSH beta mRNA inhibin is associated with a decline in GnRH receptor gene expression, suggesting that the notion that inhibin can act as a male contraceptive through selective and complete inhibition of FSH production, without effect on LH and Leydig cell function, may be mistaken. In addition, increased inhibin clearance appears to contribute to the fall in plasma inhibin levels with maturation in the male rat.

Follicular dynamics and secretion of inhibin and oestradiol-17β during the oestrous cycle of the hamster

Plasma and ovarian levels of inhibin were determined by a radioimmunoassay (RIA) at 3-h intervals throughout the 4-day oestrous cycle of hamsters. Plasma concentrations of FSH, LH, progesterone, testosterone and oestradiol-17 beta were also determined by RIAs. In addition, hamsters were injected at various times with human chorionic gonadotrophin (hCG) to determine the follicular development. The changes in plasma concentrations of FSH after injection of antisera to oestradiol-17 beta (oestradiol-AS) and inhibin (inhibin-AS) on the morning of day 2 (day 1 = day of ovulation) were also determined. Plasma concentrations of inhibin showed a marked increase on the afternoon of day 1, remained at plateau levels until the morning of day 4, then increased abruptly on the afternoon of day 4 when preovulatory LH and FSH surges were initiated. A marked decrease in plasma concentrations of inhibin occurred during the process of ovulation after the preovulatory gonadotrophin surges. An inverse relationship between plasma levels of FSH and inhibin was observed when the secondary surge of FSH was in progress during the periovulatory period. Plasma concentrations of oestradiol-17 beta showed three increase phases and these changes differed from those of inhibin. Changes in plasma concentrations of oestradiol-17 beta correlated well with the maturation and regression of large antral follicles. Follicles capable of ovulating following hCG administration were first noted at 2300 h on day 1. The number of follicles capable of ovulating reached a maximum on the morning of day 3 (24.8 +/- 0.6), and decreased by 0500 h on day 4 (15.0 +/- 1.1), corresponding to the number of normal spontaneous ovulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of Estrus and Promotion of Fertility by Prostaglandin F2.ALPHA. Administrtion in Mares.

To reduce the intervals from Parturition to conception in normal multiparous mares and to promote the fertility in mares with reproductive failures, 13 mares, a total of 17 cases, were intramuscularly injected with prostaglandin F2α (PG) in the luteal phase. Ten mares came into estrue after the first injection of 5 mg of PG, whereas 3 mares required two or three PG treatments to induce estrus. Estrus was induced 5-8 days after PG treatment in 10 out of 14 cases that showed signs of estrus. The duration of estrus was 3.9 days on the average and 11 out of 17 cases ovulated 8-12 days after PG treatment. The number of matings was 1-5 times during the induced estrus and 11 mares conceived. A “star-like layering of the folds” in the uterine cavity appeared 2-6 days after PG treatment, and then disappeared 1-2 days before ovulation on ultrasonic monitoring. The plasma levels of progesterone (P) rapidly decreased following PG treatment, whereas the plasma levels of inhibin (INH) and estradiol-17β (E2) increased after PG treatment. The plasma concentrations of LH gradually increased following PG treatment and typical prolonged LH surges were observed during the periovulatory period. In contrast, the plasma concentrations of FSH decreased after PG treatment, followed by an increase after ovulation. There was an inverse relationship between the plasma concentrations of FSH and INH. The results of the present study clearly demonstrated that treatment with PG is a useful method for reducing the intervals from parturition to conception in multiparous mares, and for improving reproductive efficiency in mares with reproductive failure.