Inhibin B in male reproduction: pathophysiology and clinical relevance

Abstract

The recent availability of speci®c inhibin assays has demonstrated that inhibin B is the relevant circulating inhibin form in the human male. Inhibin B is a dimer of an a and a b B subunit. It is produced exclusively by the testis, predominantly by the Sertoli cells in the prepubertal testis, while the site of production in the adult is still controversial. Inhibin 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 inhibin B peak in serum shortly after birth only partly correlated with an increase in serum FSH, probably re¯ecting the proliferating activity of the Sertoli cells during this phase of life. Afterwards, inhibin B levels decrease and remain low until puberty, when they rise again, ®rst as a consequence 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 administration 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 correlated with testicular volume and sperm counts. In infertile patients, inhibin 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, there are cases of Sertoli-cell-only syndrome with normal inhibin B levels. Inhibin B and FSH together are a more sensitive and speci®c marker for spermatogenesis than either one alone. However, the inhibin B concentrations are not a reliable predictor of the presence of sperm in biopsy samples for testicular sperm extraction. Suppression of spermatogenesis with testosterone and gestagens leads to a partial reduction of inhibin B in serum but it is never completely suppressed. In contrast, testicular irradiation in monkeys or humans leads to a rapid and dramatic decrease of inhibin B, which becomes undetectable when germ cells are completely absent. In summary, although inhibin B is a valuable index of spermatogenesis, the measurement of serum inhibin B levels is still of limited clinical relevance for individual patients.

The serum inhibin B concentration and reference ranges in normozoospermia

“…Inhibin B has enriched our knowledge about testicular function and regulation of the pituitary-gonadal axis in a number of genital conditions such as maturation and senescence, infertility, hypogonadism, gonadotropin administration, hormonal contraception, and testicular damage resulting from radiation or chemotherapy (1). Inhibin B is a heterodimeric glycoprotein composed of a common a subunit and a specific bB subunit (2).…”

“…Inhibin B is a heterodimeric glycoprotein composed of a common a subunit and a specific bB subunit (2). In men, the protein is produced exclusively by the testis (1). Inhibin B production is stimulated by the secretion of pituitary follicle-stimulating hormone (FSH).…”

Effect of childhood cancer treatment on fertility markers in adult male long‐term survivors

“…In recent studies, we and others have shown that Inhibin B is the best serum marker for spermatogenesis [10][11][12][13][14][15]. Inhibin B values after puberty depend on FSH secretion and are associated with sperm concentration and testicular volume not only in healthy individuals but also after chemotherapy and/or radiotherapy [16,17]. However, studies in large cohorts of adults treated for childhood cancer describing the role of Inhibin B as a male fertility marker are not available as yet.…”

The role of varicocele sclerotherapy in men with severe oligo-astheno-teratozoospermia

“…The changes in inhibin B and FSH in the follow-up period indicate rapid and reversible recovery of spermatogenesis in varicocele patients. 23,36 These rapid changes may be attributed to the younger age of patient studied compared to the study by Byrd et al 37 In addition, the shorter Table 2 Semen parameters before and after 6-month follow-up examinations in both the patient and control groups Antegrade sclerotherapy and varicoceles MA Ghanem et al 869 duration of varicocele intervention and the grade I varicoceles of the majority of the patients, which do not lead to permanent spermatogenesis damage, may be related to this rapid changes. Despite the encouraging sperm improvement after AS, the rate of natural conception is still lower than that reported after surgical repair.…”