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

Abstract

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.

Figures

Figure 1

Serum levels of FSH vs. inhibin B in normal men (black symbols), men with IHH (gray symbols), and agonadal men (open symbols). Panel A (circles) depicts FSH and inhibin B in a normal sex steroid milieu (agonadal men on physiological T replacement and IHH men on pulsatile GnRH therapy). Panel B (squares) depicts FSH and inhibin B in a castrate sex steroid milieu (normal men and IHH men on GnRH both receiving high-dose KC; agonadal men off T replacement). The inset in each panel depicts the log-transformed data revealing a logarithmic rather than a linear relationship in both a normal and castrate sex steroid milieu. The hatched area in each panel represents the normal range for FSH and inhibin B in adult men.

Figure 2

Changes in FSH and inhibin B when gonadal sex steroids are suppressed or withdrawn. Subjects from all three groups have been combined and then divided into quintiles according to their baseline serum inhibin B concentrations. The data are plotted at the mean FSH and inhibin B for each quintile in a normal sex steroid milieu at baseline (circles) and after a castrate sex steroid milieu has been established (squares). The arrows connect the paired data; the hatched area represents the normal range for FSH and inhibin B in adult men.