Inhibin B in male reproduction: pathophysiology and clinical relevance

The recent availability of specific inhibin assays has demonstrated that in hibin B is the relevant circulating inhibin form in the human male. Inhibin B is a dimer of an alpha and a beta (B) subunit. It is produced exclusivel y by the testis, predominantly by the Sertoli cells in the prepubertal test is, while the site of production in the adult is still controversial. Inhib in B controls FSH secretion via a negative feedback mechanism. In the adult , inhibin B production depends both on FSH and on spermatogenic status, but it is not known in which way germ cells contribute to inhibin B production . The regulation of inhibin B production changes during life. There is an i nhibin B peak in serum shortly after birth only partly correlated with an i ncrease in serum FSH, probably reflecting the proliferating activity of the Sertoli cells during this phase of life. Afterwards, inhibin B levels decr ease and remain low until puberty, when they rise again, first as a consequ ence of FSH stimulation and then as a result of the combined regulation by FSH and the ongoing spermatogenesis. In the adult, serum inhibin B shows a clear diurnal variation closely related to that of testosterone. The admini stration of FSH increases the secretion of inhibin B in normal men, but is much more pronounced in males with secondary hypogonadism. The treatment of infertile men with FSH, however, does not result in an unequivocal inhibin B increase. There is a clear inverse relationship between serum inhibin B and FSH in the adult. Serum inhibin B levels are strongly positively correl ated with testicular volume and sperm counts. In infertile patients, inhibi n B decreases and FSH increases. In general, there is very good correlation with the degree of spermatogenetic damage, with the arrest at the earlier stages having the lowest inhibin B levels. However, for unknown reasons, th ere are cases of Sertoli-cell-only syndrome with normal inhibin B levels. I nhibin B and FSH together are a more sensitive and specific marker for sper matogenesis than either one alone. However, the inhibin B concentrations ar e not a reliable predictor of the presence of sperm in biopsy samples for t esticular sperm extraction. Suppression of spermatogenesis with testosteron e and gestagens leads to a partial reduction of inhibin B in serum but it i s never completely suppressed. In contrast, testicular irradiation in monke ys or humans leads to a rapid and dramatic decrease of inhibin B, which bec omes undetectable when germ cells are completely absent. In summary, althou gh inhibin B is a valuable index of spermatogenesis, the measurement of ser um inhibin B levels is still of limited clinical relevance for individual p atients.