Changes in serum inhibin B during normal male puberty

OBJECTIVE: In adult men, inhibin B (InhB) regulates FSH secretion by a negative feedback. The aims of this study were to evaluate the changes of InhB during puberty in the male and the relationship between InhB and FSH, LH, testosterone and testicular volume. DESIGN: Cross-sectional study. METHODS: InhB was measured using a two-site ELISA in 100 healthy boys subdivided by their pubertal development according to Tanner into five groups of 20. RESULTS: During puberty we observed an increase of InhB level (G1 = 84.3 pg/ml, G3 = 132.2 pg/ml, G5 = 206.1 pg/ml). In G1, InhB correlated positively with FSH (P = 0.0001), LH (P = 0.005), testosterone (P = 0.001) and testicular volume (P = 0.007); in G5, InhB correlated inversely with FSH (P = 0.001) and LH (P = 0.045) and directly with testicular volume (P = 0.013). The multivariate analysis demonstrated that: in G1, FSH is the most important, and testosterone the second most significant, stimulus for InhB increase; in G2 only FSH has a positive effect on InhB variation; in G3 only mean testicular volume fits the model (G1-G3: InhB dependent variable); considering the FSH dependent variable, in G4, InhB is the most important stimulus for FSH decrease and mean testicular volume is a secondary directly proportional variable; in G5, only InhB shows a significant inverse relationship with FSH. CONCLUSIONS: During puberty there is a regular increase of InhB. In the first phases of gonadal maturation, InhB and FSH correlate positively, while in mid-late stages the relationship is inverse. We found that in mid-puberty (G3-G4), the serum concentration of InhB increases, as its inverse relationship with FSH is being established and hence spermatogenesis.     

Gonadotropin secretory dynamics during puberty in normal girls and boys

To determine the most useful index of pubertal gonadotropin secretion we measured spontaneous LH and FSH levels every 20 min for 24 h and the LH and FSH responses to LHRH in a total of 37 girls and 30 boys representing each of the 5 stages of puberty. Mean 24-h LH and FSH levels rose significantly with increasing pubertal stage in both girls and boys. LH peak amplitude increased significantly with increasing pubertal stage for both sexes, whereas FSH peak amplitude did not. LH and FSH peaks were present throughout the 24-h period in all children, but the frequency did not change significantly with increasing pubertal stage. Mean gonadotropin levels, peak amplitudes, and peak frequencies tended to be higher at night from pubertal stages 1-4 of puberty. There were no significant sex differences in mean LH, LH peak amplitude, or LH peak frequency. The LHRH-stimulated peak LH to peak FSH ratio was greater in boys than girls during pubertal stages 1-3 and was less useful in distinguishing pubertal from prepubertal boys. For girls, the most accurate index of pubertal gonadotropin secretion was a LHRH-stimulated peak LH to peak FSH ratio greater than 0.66, which detected 96% of the pubertal girls with no false positives. For boys, the most accurate index was a maximum spontaneous nighttime LH level of 12 IU/L or more, which detected 90% of the pubertal boys with no false positives. We conclude that there are important sex differences in the gonadotropin responses to LHRH during puberty, and that criteria for the onset of pubertal gonadotropin secretion should be sex specific.     

Sexual dimorphism in circulating monomeric and dimeric inhibins in normal boys and girls from birth to puberty

BACKGROUND AND OBJECTIVE: Inhibins are peptides, mainly of gonadal origin, that suppress FSH production. Dimeric forms of inhibin (A and B) have been proposed as peripheral markers of Sertoli and granulosa cell function. The aim of this study was to establish the relationship between circulating dimeric and monomeric inhibins, and gonadotrophins and sex steroids, in normal boys and girls from birth to puberty. SUBJECTS: One hundred and forty-six normal children (females: 57; males: 89) were studied. MEASUREMENTS: Serum LH and FSH were measured by an immunofluorometric assay. Serum oestradiol and testosterone were measured by radioimmunoassay. Serum inhibin A and B, and Pro-alphaC, were measured by specific two-site enzyme-linked immunosorbent assays. RESULTS: In boys from birth to 6 months of age, the mean serum inhibin B concentration was as high (477 +/- 53.7 ng/l) as that found at puberty (400 +/- 70.2 ng/l). After the first year, inhibin B gradually decreased to reach its lowest concentration (153 +/- 23.6 ng/l) at age 4-6 years. At approximately age 10, it rose progressively to reach pubertal concentrations. Pro-alphaC showed a similar pattern but at lower concentrations. Inhibin A was not detected at any age. In girls from birth to 6 months, inhibin B levels (83.0 +/- 18.3 ng/l) were approximately 50% lower than those found at puberty (181 +/- 25.7 ng/l). After 6 months of age, these levels dropped (17.5 +/- 1.6 ng/l) and remained low until the prepubertal years. Thereafter, they increased to pubertal concentrations. The serum inhibin A concentration after birth (29.9 +/- 8.7 ng/l) was similar to that found at puberty (18.3 +/- 5.7 ng/l); after 6 months, it fell to undetectable levels until the prepubertal years. CONCLUSION: The sex difference in serum levels of gonadotrophins is associated with sex differences in the levels and proportions of circulating dimeric and monomeric inhibins.     

Spontaneous growth hormone secretion increases during puberty in normal girls and boys.

To test the hypothesis that GH secretion increases during puberty, we measured GH levels in samples obtained every 20 min for 24 h from 132 normal children and adolescents. In both girls and boys, GH levels increased during puberty. The increase in mean levels was earlier in girls than boys, was most evident at night, and was due to increased pulse amplitude rather than a change in pulse frequency. The mean nighttime GH level in girls with bone ages (BA) greater than 12 to 14 yr were significantly greater than the mean level in girls with BA less than 8 yr (7.3 +/- 3.0 vs. 3.4 +/- 1.7 micrograms/L; P less than 0.01) and were greatest at breast stage 3 (7.9 +/- 2.5 micrograms/L). GH pulse amplitude increased significantly before pubertal onset in girls and was significantly greater at BA greater than 12 to 14 yr than at BA of 8 yr or less (13.9 +/- 6.0 vs. 7.9 +/- 4.8 micrograms/L; P less than 0.01) and greatest at breast stage 3 (15.0 +/- 6.3 micrograms/L). The pubertal increase in GH secretion was delayed in boys compared to girls, with the lowest mean 24-h GH and mean nighttime GH values in boys with BA greater than 8 to 11 yr. The mean nighttime GH level at BA greater than 11 to 13 yr in boys was significantly greater than that in the boys with BA greater than 8 to 11 yr (5.8 +/- 2.9 vs. 3.5 +/- 2.1 micrograms/L; P less than 0.05) and was greatest at a testicular volume of more than 10 to 15 mL (6.5 +/- 2.0 micrograms/L). The mean nighttime GH pulse amplitude in boys was significantly greater at BA greater than 11 to 13 yr than at BA greater than 8 to 11 yr (13.9 +/- 5.7vs. 7.3 + 2.6 micrograms/L, P less than 0.05) and was greatest at a testicular volume greater than 20 mL (15.8 +/- 12.0 micrograms/L). The mean nighttime GH levels correlated inversely with body mass index in both sexes, although the correlation achieved statistical significance only for the girls, being stronger in breast stage 3 to 5 girls (r = -0.57 P = 0.0007; n = 32) than in stage 1 and 2 girls (r = -0.38; P = 0.03; n = 32). These observations in normal adolescents emphasize the importance of interpreting spontaneous GH levels in short children in relation to normative data appropriate for sex, body mass, and bone age or pubertal stage.     

Serum inhibin B levels during male childhood and puberty

Inhibin B is a testicular peptide hormone that regulates FSH secretion in a negative feedback loop. In males serum levels of inhibin B are detectable throughout life with prominent changes in the first year of life and during puberty. Serum inhibin B is normally detectable throughout childhood where it is a direct marker of the presence and function of Sertoli cells. The inhibin B analysis has proven useful in the diagnosis of patients with non-palpable testes. Undetectable or low inhibin B levels are observed in boys with either congenital or acquired absence of testicular tissue whereas normal or near-normal levels are seen in cryptorchidism and disorders with preserved Sertoli cell function in spite of absence of germ cells or impaired androgen biosynthesis or action. During puberty a developmental change in the regulation of serum inhibin B occurs. In contrast to childhood inhibin B levels, inhibin B production in adult men is dependent on the presence of certain germ cells in the seminiferous tubules, most likely involving the pachytene spermatocytes and early spermatids. Thus, in adult men serum inhibin B levels are closely related to spermatogenesis with undetectable or low levels observed in SCO syndrome and early stage spermatogenic arrest whereas normal or near normal levels are observed in men with late stage spermatogenic arrest or obstructive forms of azoospermia. These clinical findings are in accordance with immuno-histological studies of the expression of inhibin B subunits in human testis.     

Change in cortical bone density and its distribution differs between boys and girls during puberty

CONCEPT: Postmenarchal girls and premenopausal women have 3-4% higher cortical bone density (CoD, milligrams per cubic centimeter), compared with postpubertal boys and men, respectively. Females' denser cortical bone is thought to serve as a calcium reservoir for reproductive needs. However, prospective data are lacking that describe CoD development and bone mineral density distribution during puberty in both sexes. OBJECTIVE: Thus, our objectives were to assess maturity and sex differences in the 20-month change of CoD and radial distribution of bone mineral density (RDBMD, milligrams per cubic centimeter) in early-, peri-, and postpubertal girls and boys. Maturity groups were based on change in menarcheal status (girls, n = 68) and pubic hair stage (Tanner) (boys, n = 59). Peripheral quantitative computed tomography was used to measure CoD and RDBMD at the tibial middiaphysis. RESULTS: The increase in average CoD was 1.9% [22.8 mg/cm(3); 95% confidence interval (CI), 10-36], 2.8% (33.8 mg/cm(3); 95% CI, 21-47), and 1.5% (55.0 mg/cm(3); 95% CI, 17-93) greater in early, peri-, and postpubertal girls, compared with boys, respectively. Analysis of RDBMD revealed that the change in density distribution varied across pubertal groups in girls. Across puberty, all girls showed an increase in the high density midcortical region, whereas only peripubertal girls showed an increase in the lower density subcortical region. A sex-difference in RDBMD change was noted within early and peripubertal groups. CONCLUSIONS: Our findings of sexual dimorphism in CoD development give support to the hypothesis that female bone deposits calcium for reproductive needs by consolidation of cortical bone during puberty.     

Secretion of inhibin A and inhibin B during pregnancy and early postpartum period in Japanese monkeys

In order to determine the profiles and sources of inhibin A and inhibin B during pregnancy in Japanese monkeys, serum samples were collected from eight monkeys for measuring concentrations of both inhibins by enzyme-linked immunosorbent assay. The term placenta was used for the localization of inhibin α-, βA-, and βB-subunits by immunohistochemistry. Serum concentrations of inhibin A showed a significant rise at the second quarter and maintained its level until term. Serum concentrations of inhibin B gradually increased until the fourth quarter. The concentration of both inhibins abruptly declined after delivery to the nonpregnant level. Positive staining of inhibin α-, βA-, and βB-subunits was observed in syncytiotrophoblast in the placenta by immunohistochemistry. These results demonstrated that large amounts of both dimeric inhibins are secreted from the placenta of Japanese monkeys.     

Salivary testosterone levels in normal boys at puberty

Salivary testosterone (Salivary-T) was measured in 133 normal boys at puberty (8-14 years old) and 21 adult males (24-36 years old) by using radioimmunoassay. Also, a simultaneous measurement was performed on salivary-T and serum total testosterone (Total-T) and free testosterone (Free-T) in order to study the correlation between saliva and serum. The results were summarized as follows: (1) Good correlations were observed in the values between Salivary-T and Total-T or Free-T. The correlation coefficient value was 0.54 between Salivary-T and Total-T, 0.84 between Salivary-T and Free-T when measured by DPC kit. Correlation coefficient value was 0.59 between Salivary-T by Wien kit and Total-T by DPC kit, also 0.77 between Salivary-T by Wien kit and Free-T by DPC kit. (2) Salivary-T, in the mean level, increased by age. The most rapid increase of Salivary-T was observed at 13 years of age. (3) Diurnal change of Salivary-T was observed at 13 years of age through adult age. Salivary-T level was highest in the morning and declined toward evening. (4) These results suggest that Salivary-T measurement was highly reliable and applicable for use in the monitoring of androgen status.     

Serum inhibin concentrations rise throughout normal male and female puberty

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.     

Changes in serum insulin-like factor 3 during normal male puberty

CONTEXT: Insulin-like factor 3 (INSL3) is produced by the Leydig cells, and in adults, its secretion is dependent on the state of differentiation of these cells, which, in turn, is dependent on LH. However, the secretion and regulation of INSL3 during puberty is unknown. OBJECTIVE: Our objective was to evaluate INSL3 concentrations during normal male puberty and the relation of INSL3 to LH, FSH, and testosterone. DESIGN AND SETTING: We conducted a cross-sectional study from January to December 2005 at academic clinics. PATIENTS: Participating in the study were 75 healthy male subjects aged 9.5-17.5 yr, homogeneously distributed into five pubertal groups of 15 according to Tanner stages. MAIN OUTCOME MEASURES: We assessed mean testicular volume and LH, FSH, testosterone, and INSL3 concentrations in relation to age and pubertal stage. RESULTS: We observed an increase of INSL3 and LH levels from Tanner stage 2 to 4, and an increase of FSH from stage 2 to 3. Testosterone levels increased from stage 3 to 4. No differences were seen for all measured hormones between stages 4 and 5. The increase in INSL3 seemed therefore to anticipate the increase in testosterone. However, INSL3 plasma concentrations at pubertal stages 4 and 5 are about one fourth of adult levels, whereas FSH, LH, and testosterone reached adult levels by stage 4. Positive significant correlations were found between INSL3 and LH for all pubertal stages. CONCLUSIONS: This study provides information on the physiological dynamics of INSL3, showing that the serum concentrations of this hormone increased progressively throughout puberty under the differentiating action of LH on Leydig cells. INSL3 is therefore confirmed to represent a marker of Leydig cell differentiation and function. However, a prolonged exposure to LH seems to be necessary to reach INSL3 concentrations of adults. A possible use of INSL3 in puberty disorders is promising.     

Secretion of inhibin A and inhibin B throughout pregnancy and the early postpartum period in chimpanzees

Plasma concentrations of inhibin A and inhibin B during pregnancy and early lactation in chimpanzees were determined by enzyme-linked immunosorbent assay (ELISA). Plasma samples were taken from five pregnant chimpanzees at 6-9, 10, 20 and 25 weeks of pregnancy, and following parturition. Throughout pregnancy and the early postpartum period, circulating inhibin A and inhibin B concentrations remained low, at similar levels to those during the normal menstrual cycle in chimpanzees. Concentrations of inhibin A in the placental homogenate were high enough to be measured by the ELISA and by bioassay, whereas circulating inhibin bioactivities in late pregnancy were too low to be measured. Plasma concentrations of FSH remained low with no significant changes throughout pregnancy and the postpartum period. Plasma concentrations of oestradiol-17beta and progesterone at 25 weeks of pregnancy were much higher than normal menstrual cycle levels. It was concluded that in chimpanzees the levels of circulating inhibin A and inhibin B remained low throughout pregnancy and the early postpartum period, and that the concentrations of bioactive dimeric inhibin did not increase towards the end of pregnancy. The suppression of circulating FSH levels during pregnancy is suggested to be controlled by steroid hormones that increased significantly in late pregnancy, and the present findings further suggest that the secretory pattern and role of inhibin during pregnancy in chimpanzees may be different from that in human and other primates.     

Changes in plasma concentrations of inhibin A and inhibin B throughout sexual maturation in the male chimpanzee

Profiles of circulating plasma inhibin A and inhibin B during sexual maturation in male chimpanzees were investigated by using two-site enzyme-linked immunoassay (ELISA). Plasma concentrations of testosterone and pituitary gonadotropins were also measured. Concentrations of inhibin B, testosterone, luteinizing hormone (LH) and prolactin increased with age throughout prepuberty to adulthood, whereas inhibin A level was low and there were no age-related changes in concentrations of either inhibin A and follicle-stimulating hormone (FSH). Inhibin B showed an inverse correlation with FSH in adult (7 years or order) but not in immature (6 years or younger) male chimpanzees. There was no correlation between plasma levels of FSH and testosterone throughout the period of sexual maturation. However, testosterone levels were positively correlated with inhibin B levels. These results suggest that circulating inhibin B is involved in the regulation of FSH secretion after puberty in adult male chimpanzees, and also that circulating inhibin B is an important form of inhibin as a marker of Sertoli cell function in adult male chimpanzees.     

Serum insulin-like factor 3 levels during puberty in healthy boys and boys with Klinefelter syndrome

CONTEXT: Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development. OBJECTIVE: The objective of the study was to characterize changes in INSL3 levels during spontaneous puberty in healthy boys, boys with aromatase inhibitor-induced hypergonadotropic hyperandrogenism, and boys with Leydig cell dysfunction. DESIGN: This was a prospective clinical study. SETTING: The study was conducted at a university hospital pediatric endocrinology outpatient clinic. PATIENTS: Patients included 30 healthy boys with idiopathic short stature (ISS) aged 9.0-14.5 yr and 14 boys with Klinefelter syndrome (KS) aged 10-13.9 yr. Intervention: In ISS boys, intervention included aromatase inhibitor letrozole or placebo for 24 months. MAIN OUTCOME MEASURES: Serum INSL3 levels in relation to bone age, Tanner pubertal stages, and LH and testosterone levels were measured. RESULTS: Onset of puberty was associated with a significant increase in INSL3 levels from 0.06 +/- 0.01 ng/ml at Tanner G1 to 0.32 +/- 0.16 ng/ml at G2 (P < 0.0001). Adult INSL3 levels (> or = 0.55 ng/ml) were attained at bone age 13-14 yr. ISS boys with letrozole-induced hypergonadotropic hyperandrogenism had, after 12 months of therapy, higher INSL3 levels than did placebo treated (0.85 +/- 0.54 vs. 0.26 +/- 0.17 ng/ml, P < 0.01). In KS boys during spontaneous puberty, after an initial increase similar to that in healthy boys, INSL3 concentrations leveled off despite hyperstimulation by LH. Positive correlations occurred between serum INSL3 and LH and between INSL3 and testosterone levels in all three groups (P < 0.0001). CONCLUSIONS: In boys, the Leydig cell-specific hormone INSL3 may serve as a new marker for onset and progression of puberty. Pubertal increase in INSL3 levels seems to depend on LH. In KS subjects, INSL3 concentrations indicate Leydig cell dysfunction from midpuberty onward.     

Biochemical markers of bone turnover in girls during puberty

OBJECTIVES Bone turnover and the rate of bone growth increase dramatically during puberty. A number of new assays for the estimation of bone resorption and formation rates have been developed over recent years, and puberty acts as a convenient model for evaluation of these measurements. The aim of this study was to explore the interrelationships between pubertal development, biochemical markers of bone turnover, Insulin-like growth factor I and oestradiol in healthy pubertal girls. SUBJECTS Ninety-one healthy girls (ages 11·6–15·5 years) were studied. All subjects were apparently healthy, and were not taking medications known to influence calcium homeostasls. Breast examination was performed to assess pubertal stage according to Tanner. The adult reference range for biochemical markers of bone turnover was obtained from concurrent studies on 42 healthy premenopausal women ranging in age between 20 and 45 years. DESIGN AND MEASUREMENTS Blood samples were obtained from subjects between 0800 and 1000 h. Urine samples were collected between 1330 and 1600 h. We measured total and bone specific alkaline phosphatase, osteocalcin, and type I procollagen carboxyterminal pro-peptide as markers of bone formation. Tartrate resistant acid phosphatase, carboxyterminal pyridinoline cross-linked telopeptide, creatinine corrected urinary deoxypyr-Idlnoline, immunoreactive urinary pyrldinolines, and urinary galactosyl hydroxylysine were measured as markers of bone resorption. RESULTS Bone turnover as reflected by each of the markers was maximal in mid puberty (breast Tanner stages II and III) and decreased towards adult levels in late puberty (P < 0·001). However, the magnitude of the mid-pubertal increase differed between markers. In particular, the pubertal increase In levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline were higher than the Increase shown by the other markers. All markers were significantly lower after the menarche. Circulating insulin-like growth factor I and Insulin like growth factor binding protein-3 were not important determinants of pubertal changes In bone turnover. In contrast, there was a significant negative correlation between oestradiol and all markers of bone formation and resorption during puberty. CONCLUSIONS The greater pubertal increase in levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline suggests that these markers may be relatively more sensitive as indicators of skeletal health during puberty. The differences between markers may reflect differences in the bone specificity of the analytes, or differing mechanisms of production and clearance. The negative correlation between oestradiol and markers of bone resorption and formation suggests that this hormone may be responsible for the reduction in bone turnover in late puberty.     

Nocturnal secretory dynamics of inhibin B and testosterone in pre- and peripubertal boys

To investigate the secretory dynamics of testosterone and inhibin B, we collected samples every 20 min from 2000 h to 0800 h in 20 boys. Boys in group 1 (n = 5) were aged less than 8 yr, group 2 (n = 5) were aged more than 8 yr but 1.5 yr or more before pubertal onset, group 3 (n = 5) were studied 1.0 yr or less before pubertal onset, and group 4 (n = 5) were in early puberty. Testosterone increased after midnight in peripubertal boys, coinciding with the onset of LH pulsatility, and showed a pulsatile pattern in 6 of 10 of these boys. Cross-correlation analysis indicated significant temporal coupling between LH and testosterone. Inhibin B was higher in groups 3 and 4, compared with groups 1 and 2 (P < 0.01) and showed a downward trend overnight with no evidence of pulsatility and no evidence of short-term interactions with LH, FSH, or testosterone. Inhibin B and LH nocturnal means were both inversely correlated with time before pubertal onset (r(s) > or = -0.85, P < 0.01). Only LH nocturnal mean and amplitude, respectively, contributed independently to prediction of testosterone and inhibin B nocturnal means, explaining 71 and 65% of their variability. We conclude that both testosterone and inhibin B are related to nocturnal LH release in peripubertal boys but over different time scales.     

Early puberty in girls

Early puberty is not well defined in paediatric endocrinology. This chapter reviews the current insights on definitions, patient groups and treatment modalities in girls with early puberty. It is concluded that there is no clear evidence for a beneficial effect of gonadotrophin releasing hormone agonist (GnRHa) treatment in auxological terms. A clinical approach is presented, including both auxological and psychological items. Further research is needed to answer the question of whether early puberty should be treated with GnRHa.     

Changes in circulating and testicular levels of inhibin A and B and activin A during postnatal development in the rat

This study describes the testicular levels of inhibin/activin subunits by Northern analysis and in situ hybridization and serum and testicular levels of inhibins A and B and activin A by enzyme linked immunosorbent assays (ELISA) during postnatal development in the rat. We show that serum inhibin A levels are less than 4 pg/ml throughout postnatal life. Serum inhibin B levels peak at 572 +/- 119 pg/ml (mean +/- se) at d 40 post partum (pp) before falling to 182 +/- 35 pg/ml in mature males. Serum activin A decreases from 294 +/- 29 pg/ml at d 6 to 132 +/- 27 pg/ml at maturity. Within the testis, inhibin A levels fall from 0.330 +/- 0.108 ng/g at d 15 to less than 0.004 ng/g at maturity. Inhibin B levels peak at 43.9 +/- 4.2 ng/g at d 6 before falling to 1.6 +/- 0.13 ng/g at maturity. Testicular activin A levels fall from 18.6 +/- 2.2 ng/g at d 6 to 0.094 +/- 0.013 ng/g at maturity. Northern profiles of testicular inhibin/activin subunits correlate with immunoreactive levels demonstrated by ELISA. In situ hybridization suggests that beta(A) and beta(B) subunit expression is largely restricted to the seminiferous tubule, particularly Sertoli cells, spermatogonia, and primary spermatocytes. These data support the view that inhibin B is the major inhibin in the male rat and that levels relate to Sertoli cell number and activity. Furthermore, the demonstration of high local concentrations of activin A during the period of Sertoli cell proliferation and the onset of spermatogenesis support its proposed role because a modulator of testicular development and function.