Inhibin-B levels in healthy young adult men and prepubertal boys: is obesity the cause for the contemporary decline in sperm count because of fewer Sertoli cells?

Inhibin-B is a heterodimeric glycoprotein produced by Sertoli cells. Although inhibin-B levels are low when seminiferous tubules are damaged, studies in normal monkeys reveal that inhibin-B levels also correlate positively with Sertoli cell number. In this study, we measured inhibin-B levels in healthy young adult men aged 18-24 years and in prepubertal boys aged 5-9 years in relation to body mass index (BMI). Inhibin-B levels declined with increasing obesity in young adult men; values were 26% lower in men who were obese compared to normal-weight men. Sex hormone-binding globulin and total testosterone, but not free testosterone, were also lower with increasing BMI; serum follicle-stimulating hormone and luteinizing hormone levels were unaffected by obesity. In prepubertal boys, by contrast, inhibin-B was unaffected by obesity. We propose that reduced levels of inhibin-B indicate that obese men have fewer Sertoli cells than men of normal weight. Moreover, normal values in obese prepubertal boys suggest that the effect of obesity on inhibin-B is established during puberty. Finally, because each Sertoli cell is thought to support a finite number of germ cells, fewer Sertoli cells in obesity may predispose to a lower sperm count in adulthood. We speculate that the escalating prevalence of obesity and insulin resistance among adolescents might negatively influence male reproductive function for the next generation.

Racial difference in circulating sex hormone-binding globulin levels in prepubertal boys.

Racial differences in disease risk (eg, osteoporosis, metabolic cardiovascular syndrome, and prostate cancer) may arise partly on a hormonal basis. While reports of racial differences in gonadal steroid hormone levels in middle-aged men have produced conflicting results, there is evidence that high sex hormone-binding globulin (SHBG) and estradiol levels are more common among young adult African American men than white men. To determine whether this difference relates to pituitary-testicular functioning or to other factors, we conducted a cross-sectional study of 47 healthy prepubertal African American and white boys aged 5 to 9 years at the time of their annual school physical examination. Height, weight, blood pressure, waist and hip circumference, and Tanner staging were determined, and a fasting blood sample was obtained. The African Americans studied were slightly older than the whites (mean +/- SD, 82.4 +/- 15.0 vs 70.5 +/- 10.3 months, P = .003). African Americans were also slightly taller and heavier and had a lower waist-to-hip ratio, but these differences could be explained by the difference in age. Mean SHBG levels were 25% higher (P = .15) in African Americans than in whites (197 +/- 104 vs 157 +/- 79 nmol/L), and when adjusted for age, values were 46 nmol/L higher among African Americans. The fifth quintile for SHBG (values > 245 nmol/L) included 1 (4.2%) of 24 whites and 8 (35%) of 23 African Americans studied (P = .003). There was no significant correlation between age, body mass index, waist circumference, or fasting insulin and SHBG. Total testosterone, the free androgen index, and dehydroepiandrosterone increased with age in both groups, but after adjusting for age, no racial differences were found. Estradiol, estrone, and inhibin B levels, as well as systolic and diastolic blood pressures, were also comparable in both groups. We conclude that high levels of SHBG are more common among African American than in white boys and hypothesize that this difference and its effect on the ratio between bound and free steroid hormones may contribute to racial differences in disease risk in adult men.