Figure 1.

Schematic of the hypothalamic-pituitary gonadal axis in normal and GnRH-deficient men. In normal men, T and E₂ can exert negative feedback at both the hypothalamus and pituitary. In contrast, men with congenital GnRH deficiency lack endogenous GnRH secretion. However, their pituitary-gonadal axis can be normalized with pulsatile GnRH therapy. Because the dose and frequency of exogenous GnRH are experimentally controlled, this model represents a hypothalamic clamp. Therefore, any effect on gonadotropin secretion of altering gonadal steroids in such GnRH-deficient men can reflect only a pituitary site of action. Thus, a hypothalamic site of action of sex steroids can be inferred whenever there is a difference in the gonadotropin responses of normal and GnRH-deficient men to alterations in their sex steroid milieu.