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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

Reproductive Endocrine Unit of the Department of Medicine (P.A.B., F.J.H., A.A.D., T.R., W.F.C., N.P.) and the Department of Biostatistics and the General Clinical Research Center (H.L.), Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Nelly Pitteloud, M.D., Reproductive Endocrine Unit, BHX5, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: pitteloud.nelly{at}mgh.harvard.edu.

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.

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				N. Pitteloud, A. A. Dwyer, S. DeCruz, H. Lee, P. A. Boepple, W. F. Crowley Jr., and F. J. Hayes The Relative Role of Gonadal Sex Steroids and Gonadotropin-Releasing Hormone Pulse Frequency in the Regulation of Follicle-Stimulating Hormone Secretion in Men J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2686 - 2692. [Abstract] [Full Text] [PDF]