Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone in men across the full spectrum of seminiferous epithelium function

Context and objective: Our aim was to explore the relative roles of gonadal sex Steroids and Inhibin B in the regulation of FSH across a spectrum of seminiferous epithelium function.

Subjects: The study included three groups: group I, healthy men (n = 31); group II, men with idiopathic hypogonadotropic hypogonadism receiving pulsatile GnRH (n = 12) selected to represent a spectrum of seminiferous tubular development, testicular size, and baseline Inhibin B levels; and group III, men with functional anorchia (n = 3) receiving testosterone replacement.

Design: Subjects were studied before and after 3 d of acute sex steroid withdrawal.

Setting: The study was conducted at the Mallinckrodt General Clinical Research Center of Massachusetts General Hospital.

Interventions: Acute biochemical castration was achieved using high-dose ketoconazole (groups I and II) or withdrawal of androgen therapy (group III).

Main outcome measures: The relationship between FSH and Inhibin B in both normal and castrate sex steroid milieu was measured.

Results: In both normal and castrate sex steroid milieus, there was a negative relationship between Inhibin B and FSH, best described by a logarithmic model. Acute biochemical castration resulted in the most dramatic increases in FSH in men with the lowest baseline Inhibin B levels.

Conclusions: We came to the following conclusions: 1) in the human male, Inhibin B is the principal gonadal feedback regulator of FSH secretion unless seminiferous tubular function is severely compromised, and a logarithmic model best describes this relationship; and 2) sex steroid inhibition of FSH secretion is most apparent when serum Inhibin B levels fall well below the normal range.