Reversibility of GnRH Agonist-Induced Inhibition of Testicular Function: Comparison Between Rat, Monkey and Man

Abstract

Gonadotropin-releasing hormone (GnRH) agonists and antagonists bind to hypophyseal GnRH receptors and thereby inhibit gonadotropin release (Nestor et al. 1984). However, the mechanism of blocking gonadotropin release for GnRH agonists is different from that for antagonists. GnRH agonists initially stimulate LH and FSH secretion, but this is quickly followed by a down-regulation of pituitary GnRH receptors. The GnRH-agonist-receptor complex is internalized by the gonadotropic cells (Duello et al. 1983) and decreased secretion of gonadotropic hormones results (Loumaye and Catt 1983). In contrast, GnRH antagonists bind firmly to the GnRH receptor and inhibit gonadotropin synthesis and release by blocking the action of hypothalamic GnRH (Heber et al. 1982; Loumaye et al. 1984). As a consequence of the induced hypogonadotropism, testosterone production is decreased and chronic treatment with GnRH analogues severely impairs or completely suppresses spermatogenesis in primates (Weinbauer and Nieschlag 1985) and rats (Labrie et al. 1980). Since rat Ley dig cells have receptors for GnRH agonists, additional direct effects of the GnRH analogues on the testes of this species have been considered (Cao et al. 1982; Hsueh et al. 1983).