Desensitization of both luteal and pituitary function in baboons with nafarelin, a potent LH-RH agonist

Acute responsiveness in vivo of the baboon corpus luteum to a course of twice daily injections of human chorionic gonadotropin (hCG) has been studied with and without concomitant injections of nafarelin, a potent luteinizing hormone-releasing hormone (LH-RH) agonist. HCG injection alone caused an acute (1 hour) rise in circulating levels of progesterone (P), confirmed to be a direct effect at the luteal level, since no change in circulating levels of endogenous LH was detected. When hCG was coadministered with a low dose of nafarelin (50 micrograms per injection), circulating levels of LH rose, but the rise in serum P levels was blunted. However, when hCG was coadministered with a high dose of nafarelin (250 micrograms per injection), serum LH levels rose only in response to the first injection and serum levels of P were not elevated, suggesting a desensitization of the pituitary to the LH-RH agonist and of the corpus luteum to the hCG. The profile of luteal P during the luteal phase in response to combined treatment with hCG and nafarelin also reflected these effects, being intermediate between vehicle controls and hCG treatment alone. This first demonstration of a luteal desensitization to gonadotropin by an LH-RH agonist in primates may account for previously noted successful interception of pregnancy in baboons treated with these agents.