Serum gonadotropin, sex steroid, and immunoreactive inhibin levels in the first two years of life.

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.

Follicular arrest during the midfollicular phase of the menstrual cycle: a gonadotropin-releasing hormone antagonist imposed follicular-follicular transition.

The functional dependency of the dominant follicle on pulsatile gonadotropin inputs was evaluated by using a GnRH antagonist as a probe. Hormonal dynamics, particularly the relationship of FSH, estradiol, and inhibin, during and after the withdrawal of GnRH receptor blockade achieved by treatment with Nal-Glu GnRH antagonist (50 micrograms/kg, im) for 3 days in the midfollicular phase of the cycle (days 7-9) were ascertained. Daily blood samples were obtained for LH, FSH, estradiol (E2), progesterone, and immunoreactive inhibin (i-INH) measurements by RIA during 2 consecutive (control and treatment) cycles in 12 women. In 5 women, LH pulsatility was assessed by 10-min blood sampling for 12 h before, during, and after Nal-Glu treatment. The administration of Nal-Glu prolonged both follicular phase (14.0 +/- 0.5 vs. 19.7 +/- 0.8 days; P less than 0.0001) and total cycle length (28.1 +/- 0.5 vs. 34.1 +/- 1.2 days; P less than 0.0001). Gonadotropin suppression (50-60%) was achieved, as reflected by a marked decrease in mean LH levels (14.3 +/- 1.9 to 5.4 +/- 0.5; P less than 0.01) and LH pulse amplitude (5.5 +/- 0.7 to 2.4 +/- 0.3 IU/L; P less than 0.01) in response to Nal-Glu antagonist. The number of LH pulses was reduced (36%), but pulses remained discernible. Concentrations of FSH (10.8 +/- 1.4 to 5.9 +/- 0.4 IU/L; P less than 0.05), E2 (322.7 +/- 71.9 to 84.8 +/- 7.7 pmol/L; P less than 0.01) and i-INH (284.0 +/- 25.9 to 164.4 +/- 7.5 U/L; P less than 0.01) decreased concomitantly. Within 24-48 h of the last injection of Nal-Glu, all hormones had returned to pretreatment levels. This was followed by normal functional expression of follicular growth and maturation, as reflected by an increase in E2 and i-INH levels, timely ovulation, and normal luteal function. These findings indicate that an approximately 50% decline in gonadotropin support to the dominant follicle leads to functional arrest, but not demise, of the developing follicle(s) without triggering new folliculogenesis. The follicular apparatus retained its ability to reinitiate its original functionality once appropriate gonadotropin inputs were reinstated.

Variable androgen receptor levels in infertile men.

Labeled methyltrienelone was used to determine androgen receptor (AR) levels in cultured pubic skin fibroblasts in 40 infertile men with primary seminiferous tubule disorders and 18 normal men. LH pulse patterns and mean serum LH levels were also determined by blood sampling at 10-min intervals for 6 h. The infertile men and the normal men had similar mean receptor levels [mean, 28.1 +/- 2.0 (+/- SEM) and 24.8 +/- 1.8 fmol/mg protein, respectively]. However, 5 men with chromosomal disorders had a higher mean AR level (41.3 +/- 6.2 fmol/mg protein) than the normal men, and 5 of the remaining infertile men (14.2%) had receptor levels that were less than the minimum value in normal men. In men with idiopathic oligospermia, 19.0% had low receptor levels. Although mean serum FSH and testosterone levels were similar in the infertile men with low AR levels and in the normal men, mean LH levels were significantly elevated in this group (7.1 vs. 3.6 IU/L), the higher values being a result of increased LH pulse amplitude (mean, 5.6 vs. 2.8 IU/L). The LH-testosterone product (an index of androgen resistance) was also elevated in these men. When infertile men with low AR levels were matched with infertile men with normal receptor levels, the mean LH values were significantly elevated in the former, as was the LH-testosterone product. Testosterone values were similar in the two groups of men. After excluding subjects with chromosomal disorders, there were no significant correlations between AR levels and other indices of androgen action, such as semen volume, seminal fructose, or sex hormone-binding globulin levels. We conclude that AR levels are higher in patients with severe testicular failure associated with X-chromosome disorders. Also, AR defects were found in 19.0% of infertile men with idiopathic oligospermia. Finally, elevation of mean LH levels in men with seminiferous tubule disorders may reflect resistance to androgen action.

Dynamic changes in circulating inhibin levels during the luteal-follicular transition of the human menstrual cycle.

Dynamic changes in serum immunoreactive (ir) inhibin levels during the transition from the luteal to the follicular phase (luteal-follicular transition) were characterized during 3 consecutive cycles in 12 cycling women. Both spontaneous (first to second cycle) and GnRH antagonist-imposed premature luteolysis (second to third cycle) were evaluated. Serum FSH, LH, estradiol (E2), and progesterone (P4) levels were monitored daily by RIA for the entire study. Daily ir-inhibit levels were determined from 7 days before until 7 days after the onset of menses and from 4 days before to 10 days after the GnRH antagonist-induced bleeding by a heterologous RIA. During spontaneous luteolysis, ir-inhibin levels peaked 7 days before menses and declined in a linear fashion (r = -0.99) thereafter, reaching a sustained low level 1 day after the onset of menses. The decline of P4 and E2 levels appears to be coupled to that of ir-inhibin (r = 0.98 and r = 0.95, respectively). FSH levels showed an inverse pattern, with an acute elevation unaccompanied by LH, for 5 days before the onset of menses and reaching a plateau 2 days after. ir-Inhibin and FSH were negatively correlated (r = -0.87; P less than 0.0001). Increased LH levels did not occur until the day of menses and were negatively correlated with ir-inhibin (r = -0.50; P less than 0.05), but not E2 and P4. During the second cycle, at the midluteal phase luteolysis was induced by a single (50 micrograms/kg) im injection of a potent GnRH antagonist, [Ac-D2Nal,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA),+ ++DAla10] GnRH; an acute decline of LH and FSH levels occurred, with maximal suppressions of 51% and 35%, respectively. ir-Inhibin levels decreased rapidly (40 +/- 2.8%) in parallel with E2 and P4 during the first 24 h and continued to decline for 4 days. The inverse relationship and time course of changes between FSH and ir-inhibin levels were similar to those of the spontaneous luteal-follicular transition. Six of the 12 subjects experienced partial reversal of luteolysis; the decline of ir-inhibin and the rise of FSH during the first 2 days were arrested for 4 days, which corresponded to the rebound increases in E2, P4, and LH. The subsequent fall of ir-inhibin was followed by a rise in FSH. Both the complete and incomplete luteolysis groups exhibited an orderly follicular maturation, LH surge, and luteal function during the ensuing cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Human chorionic gonadotrophin raises serum immunoreactive inhibin levels in men with hypogonadotrophic hypogonadism.

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.

Control of inhibin production by dispersed human luteal cells in vitro.

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.

Inhibin and age in men.

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.

Circulating levels of inhibin in pregnant women at term: simultaneous disappearance with oestradiol and progesterone after delivery.

Circulating levels of immunoreactive inhibin (ir-inhibin) and its disappearance after delivery of the placenta were determined in seven pregnant women at term. Serum oestradiol (E2) and progesterone (P4) levels were measured simultaneously and served as comparisons. Fetal contributions of ir-inhibin were assessed by determining concentrations in the umbilical artery (UA) and vein (UV). Relative changes in circulating levels of ir-inhibin, E2, and P4 were compared to levels found in nonpregnant women during the early follicular phase (EFP) and mid-luteal phase (MLP) of the normal menstrual cycle. In pregnant women, ir-inhibin levels at delivery were 15- and 3-fold higher than EFP and MLP values respectively. The disappearance of all three hormones after removal of the placenta followed a bi-exponential curve with an initial, rapid component and a second, slower component. There was a highly significant positive correlation between the disappearance curves of all three placental hormones (r = 0.97, P less than 0.0001). Concentrations of ir-inhibin in the cord blood were about half that in maternal serum and without significant difference between levels in UA and UV.

Timing of ovulation by determination of the urinary luteinizing hormone surge with an enzyme-linked monoclonal antibody dipstick (OvuStick).

An enzyme-linked double monoclonal antibody dipstick for measuring luteinizing hormone in urine was tested for timing ovulation in thrice daily urine samples collected for several days around mid-cycle in 24 women undergoing artificial insemination. The assay produced information comparable to single daily serum LH measurements. The dipsticks could be used by untrained people to test their own urine as an aid to the detection of ovulation for the timing of artificial insemination or of sexual intercourse to promote or avoid conception.