Context & Objective: Our aim was to explore the relative roles of gonadal sex steroids and inhibin B (I_B) in the regulation of follicle-stimulating hormone (FSH) across a spectrum of seminiferous epithelium function.

Subjects: Group I, healthy men (n = 31); Group II, men with idiopathic hypogonadotropic hypogonadism (IHH) receiving pulsatile GnRH (n = 12) selected to represent a spectrum of seminiferous tubular development, testicular size, and baseline inhibin B levels; Group III, men with functional anorchia (n = 3) receiving testosterone (T) replacement.

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

Setting: The Mallinckrodt General Clinical Research Center of Massachusetts General Hospital.

Interventions: Acute biochemical castration was achieved using high dose ketoconazole (KC) (Groups I and II) or withdrawal of androgen therapy (Group III).

Main outcome measures: Relationship between FSH and inhibin B in both normal and castrate sex steroid milieu.

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: i) In the human male, inhibin B is the principal gonadal feedback regulator of FSH secretion unless seminiferous tubular function is severely compromised; a logarithmic model best describes this relationship. ii) Sex steroid inhibition of FSH secretion is most apparent when serum inhibin B levels fall well below the normal range.