Extrapituitary Actions of Gonadotropin-Releasing Hormone*

Abstract

Harris (1) first proposed that the anterior pituitary gland is controlled by hypothalamic releasing factors. After the subsequent purification and sequencing of gonadotropin-releasing hormone (GnRH) (2, 3) and the synthesis of potent GnRH agonists and antagonists (4, 5), many laboratories have investigated the effects of these peptides on various reproductive functions. In both males and females, administration of GnRH or its potent agonists results in sustained increases in serum gonadotropins. In women, administration of GnRH causes preovulatory-like surges of gonadotropins (6, 7). In several animal species, a single injection of GnRH induces preovulatory- like surges of LH that trigger ovulation (8–11). Since pituitary gonadotropins are essential for normal gonadal functions and hypothalamic GnRH was believed to act solely on the pituitary gland, treatment with high doses of GnRH and its agonists had been predicted to be a potential means for enhancing fertility. Paradoxically, long term administration of pharmacological doses of GnRH or potent GnRH agonists was shown to decrease a variety of female and male reproductive functions (Table 1).