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Objective: FSH causes a dose-related increase in circulating immunoreactive inhibin (INH) in the follicular phase of the menstrual cycle, while LH is the major stimulus to INH secretion by the corpus luteum. The present study was undertaken to assess whether FSH can also stimulate INH production during the luteal phase., Design: Normal volunteers were treated with a single injection of LH-free FSH (Metrodin, 150 units) or saline as control, during the early, mid- or late luteal phase of the cycle, with subsequent hormone measurements., Patients: The 21 volunteers were aged 19-29. Seven subjects given FSH and 8 controls were studied in the early luteal phase, 1-4 days post ovulation. Eight FSH treated subjects and 10 controls were studied in the midluteal phase, 5-9 days post ovulation, and 6 each, respectively, were studied in the late luteal phase., Measurements: Oestradiol (E2), progesterone (P), and INH were measured by previously described radio-immunoassays., Results: In both the early and mid-luteal phases, FSH caused a significant rise in INH (early, from 778 to 922 U/l, mid-luteal 1553 to 2090 U/l) and E2 (early 371 to 545 pmol/l, mid-luteal 528 to 636) while there was no significant change in P. No significant changes occurred in the saline treated subjects. In the late luteal phase FSH prevented the significant fall in INH seen in the controls, whilst there was no effect on E2 or P., Conclusions: It was concluded that both FSH and LH are capable of modulating inhibin production during the luteal phase of the menstrual cycle. FSH may exert its actions on the corpus luteum or alternatively on developing follicles. The present study cannot clearly distinguish between these possibilities.

Background: Inhibin is an ovarian hormone that inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. Women with granulosa-cell tumors of the ovary have elevated serum inhibin concentrations, but whether the concentrations are increased in women with other ovarian tumors is unknown., Methods: We measured serum inhibin and FSH concentrations before surgery in 212 postmenopausal women with suspected ovarian cancer and after surgery in 210 of them., Results: Eighteen of the 22 women (82 percent) with mucinous carcinomas (mucinous cystadenocarcinomas and mucinous borderline cystic tumors) of the ovary had elevated serum inhibin concentrations, whereas only 9 of the 53 women (17 percent) with serous carcinomas (serous cystadenocarcinomas and serous borderline cystic tumors) had elevated levels. Serum inhibin concentrations were also elevated in 2 of 12 women (17 percent) with clear-cell carcinomas, 4 of 26 women (15 percent) with undifferentiated carcinomas, 3 of 3 women (100 percent) with granulosa-cell tumors, and 5 of 27 women (19 percent) with other ovarian cancers. The serum concentrations of inhibin were increased in 2 of 28 women (7 percent) with nonovarian pelvic cancers and 11 of 41 women (27 percent) with benign ovarian diseases. All women but one with initially elevated serum inhibin concentrations had low values one week after surgery. Serum inhibin concentrations correlated negatively with serum FSH concentrations (P = 0.05) in women with granulosa-cell tumors but not in women with other tumors, suggesting that the inhibin secreted by tumors in the latter group has decreased biologic activity., Conclusions: Serum inhibin concentrations are elevated in most postmenopausal women with mucinous carcinomas of the ovary and in some women with other types of epithelial ovarian tumors. The concentrations fall after tumor removal.

Objective: We aimed to concurrently characterize serial changes in circulating immunoreactive inhibin (irINH) and testosterone (T) as reflections of Sertoli and Leydig cell responses to acute critical illness in man., Design: Blood samples were drawn within 24 hours of admission to an Intensive Care Unit and at weekly intervals thereafter for up to 4 weeks while the patient remained in Intensive Care Unit or after discharge to a general ward., Patients: We studied 13 male subjects with critical illness requiring intensive therapy., Measurements: Plasma levels of irINH, T, LH, FSH and sex hormone binding globulin (SHBG) were analysed in relation to (i) the severity of illness as indicated by a sepsis score, acute physiology and chronic health evaluation score, and reverse triiodothyronine (rT3) levels and (ii) the outcome of illness as determined by discharge from Intensive Care Unit and the two-month mortality., Results: Overall irINH levels remained normal and correlated negatively with rT3 (r = -0.63, P = 0.001) but not with sepsis, acute physiology and chronic health evaluation score, or gonadotrophin levels. Neither admission nor serial irINH levels significantly distinguished between the different clinical outcomes. In contrast, T levels were depressed and inversely correlated with both sepsis and acute physiology and chronic health evaluation scores (P less than 0.02), and positively with gonadotrophins (P less than 0.01), but not rT3 levels. Men eventually discharged from the Intensive Care Unit showed a rise, while those remaining showed a fall, in T levels (P = 0.02, time-course interaction). Similarly, T levels were lower in patients who died than in survivors, despite the comparable T levels on admission (P = 0.02, time-course interaction). Despite the fall in T levels, gonadotrophin levels remained inappropriately in the eugonadal range but higher in men who were discharged from Intensive Care Unit (P = 0.02, time-course interaction). FSH but not LH levels were correlated with sepsis score (P = 0.02) but not acute physiology and chronic health evaluation score or rT3., Conclusions: Sertoli cell function as judged by circulating irINH levels is much less affected by acute critical illness than is Leydig cell function as judged by circulating T levels. The suppressive effect of acute critical illness on Leydig cell function is consistent with a hypothalamic-pituitary lesion.

The production of inhibin in vitro by dispersed cells from early to mid (Days 16-19) and late stage (Day 23) human corpus luteum (CL) was examined, and the effects of human chorionic gonadotrophin (hCG), follicle stimulating hormone (FSH), oestradiol and testosterone on inhibin production were determined. Corpora lutea from five subjects in the early to mid luteal stage and three subjects in late luteal stage were dispersed with enzymes and the luteal cells cultured in medium supplemented with 5% calf serum and either FSH (1, 10 or 100 ng mL-1), oestradiol-17 beta (2.5, 5 or 10 micrograms mL-1) or testosterone (0.25, 1 or 5 micrograms mL-1) with or without hCG (1 I.U. mL-1). Cells were cultured for 1 to 3 days without changes of medium, and the concentrations of progesterone, oestradiol and immunoreactive inhibin in the medium were measured by radioimmunoassay. Cells from both types of CL produced inhibin in vitro under basal conditions, but only cells from early to mid CLs responded to hCG with a significant increase in inhibin production. Both progesterone and oestradiol production were stimulated by hCG in both groups of CL. Inhibin concentrations in the cell cultures declined with time in culture, particularly in the late CL group, whereas the concentration of steroids increased. Neither FSH, oestradiol nor testosterone significantly changed inhibin production in either CL group. It was concluded that inhibin production by human luteal cells in vitro is influenced by the age of the CL, and is dependent on LH (hCG) but not on FSH or sex steroids.

In order to determine whether serum-immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo-oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow-up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease.

Objective: Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine if changes in testicular function occur over the age range 19-60 years., Design: Single fasting blood samples were obtained between 0800 and 0900 h., Patients: Working men in a large industrial company between the ages of 19 and 60 years participated in the study., Measurements: FSH, serum immunoreactive inhibin and total testosterone were measured, the latter two as measurements of Sertoli and Leydig cell function respectively., Results: The mean baseline serum immunoreactive inhibin level was significantly lower in men from the older age groups, 31-40 years (479 U/l), 41-50 years (439 U/l) and 51-60 years (415 U/l) than in men from the youngest age group, 21-30 years (613 U/l) while serum FSH was higher in men from the older age groups, 41-50 years (3.7 IU/l) and 51-60 years (6.1 IU/l) than in men from the youngest age group, 21-30 years (2.6 IU/l). There appears to be a change in both FSH and inhibin production, consistent with a primary decline in testicular function. There was no significant difference in testosterone levels between the older age group, age 51-60 years and the younger age group, age 21-30 years. However, testosterone levels were significantly lower in the 41-50 year age group, when compared with the 21-30 year, this significance levelling out at about age 45 years., Conclusion: The data are consistent with the hypothesis that immunoreactive inhibin reflects inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men.

To characterize the changes in serum immunoreactive inhibin (INH) in the first 2 yr of life, blood samples were obtained from 46 boys (age range, 61-659 days) and 37 girls (76-666 days) undergoing minor surgery for nonendocrine related conditions. Serum levels were compared with those of simultaneously measured FSH, LH, and either testosterone (T) or estradiol (E2). In the boys, the levels of all 4 hormones fell progressively with age up to about 300 days, with a minor fall only in the second year. FSH (0.7-1.4 IU/L) was initially at the lower adult male limit, while LH (3.2-5.0 IU/L) was at the midrange. T levels (2.2-3.3 nmol/L) were in the adult female range, while INH (200-820 U/L) was in the midrange for men. In the youngest girls, FSH levels (12-26 IU/L) were frequently above the upper limit of normal for the adult follicular phase, but fell to approximately 2.0 IU/L after 300 days. LH levels (0.5-3.5 IU/L) were at the lower adult normal limit and changed little with age, while E2 levels in the youngest girls (280-550 pmol/L) were in the midfollicular range, but were generally less than 10 pM at more than 200 days. INH levels (175-260 U/L) were in the low adult range initially, but the majority were undetectable over 200 days. In the boys, significant negative correlations were observed for all 4 hormones with age, while FSH, LH, and T were positively correlated with INH. In the girls, there were weaker negative correlations of the 4 hormones with age, but no significant correlations between the gonadotropins and INH. E2 was strongly correlated with INH. Thus, the previously described early postnatal activation of the hypothalamo-pituitary-gonadal axis involves INH as well as the se steroids and gonadotropins. FSH levels in young girls were strikingly high, and INH levels were much higher in boys than girls. The low INH levels in girls may contribute to the elevated FSH seen during the period of neonatal gonadal activation.

Our experience of ovarian electrocautery for the treatment of polycystic ovarian syndrome (PCOS) in ten women is described. We found that nine responded favourably, either ovulating spontaneously or becoming more responsive to ovulation induction. There was a significant and persistent fall in serum testosterone levels, and a transient fall with subsequent rise in inhibin. We recommend that laparoscopic ovarian electrocautery is considered as an alternative to ovulation induction with gonadotrophins, in women with PCOS who fail to respond to clomiphene citrate.

Inhibin is a gonadal glycoprotein hormone involved in the regulation of FSH. To elucidate the regulation of inhibin production we investigated the acute (daily for 1 week) and chronic (9-10 months of follow-up) changes in immunoreactive inhibin, testosterone, LH and FSH levels in the serum of three hypogonadotrophic hypogonadal patients treated first with hCG alone (for 3-6 months) and then hCG combined with FSH (1-5 months). One patient was unexpectedly resistant to gonadotrophin therapy; in the other two, hCG, with or without FSH, caused a rise in inhibin and testosterone, supporting previous observations that LH, as well as FSH, plays a role in the regulation of inhibin or inhibin-related peptides in men.

Using a newly developed, sensitive, and specific RIA, we measured the serum concentrations of inhibin, together with those of FSH, LH, and sex steroids, throughout puberty in 99 boys and 102 girls attending a suburban Melbourne school. Serum inhibin levels rose from a geometric mean level of 161 U/L (range, 87-310; 67% confidence interval) at stage I puberty in boys to 442 U/L (range, 300-626) at stage V, while corresponding values in girls were 97 U/L (range, 46-204) and 231 U/L (range, 187-372), respectively. Serum inhibin concentrations were strongly correlated with age and serum FSH, LH, testosterone, and estradiol; all hormones increased in parallel in both boys and girls. After adjustment for age, the partial correlation coefficients remained significant only for testosterone in the boys. We hypothesize that gonadal inhibin production is stimulated by rising gonadotropin levels during pubertal development.

Inhibin is a peptide hormone normally produced by ovarian granulosa cells. It reaches a peak of 772 +/- 38 U per liter in the follicular phase of the menstrual cycle and is undetectable in the serum of menopausal women. To determine whether measurements of serum inhibin levels would provide a biochemical marker of the presence or progression of ovarian granulosa-cell tumors and their metastases, we measured the serum immunoreactive inhibin concentrations in six women with such tumors. Three women had been treated by hysterectomy and bilateral salpingo-oophorectomy. In the two women with residual or recurrent disease, the serum inhibin levels were abnormally elevated 5 and 20 months before the clinical manifestations of recurrence became evident. The maximal concentrations approached 3000 U per liter. The serum inhibin level remained undetectable in one patient who was disease-free for 11 years. Serum inhibin concentrations were also elevated in three women with amenorrhea and infertility that resulted from small granulosa-cell tumors. After the removal of the tumors, the serum inhibin levels in these women became normal, and fertility returned. There was a significant negative correlation between the serum concentrations of inhibin and follicle-stimulating hormone, in a manner consistent with the autonomous production of inhibin by granulosa-cell tumors. We conclude that granulosa-cell tumors produce inhibin. Since serum inhibin levels reflect the size of the tumor, measurements of inhibin can be used as a marker for primary as well as recurrent disease.