Calcium antagonists and hormone release. III. Role of calcium in the biphasic release of luteinizing hormone in response to gonadotrophin-releasing hormone in vivo.

Recent in vitro studies have demonstrated that Ca2+ plays an essential role in gonadotrophin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. In vivo, we have previously shown that verapamil, a substance known to inhibit calcium entry into cells, is capable of inhibiting basal gonadotrophin release as well as the release of luteinizing hormone and follicle-stimulating hormone (FSH) in response to an iv bolus of GnRH. We have examined the effects of calcium antagonists on the two phases of pituitary LH release in response to constant GnRH infusion in normal subjects. In 6 men, constant infusion of GnRH (0.2 microgram/min x 4 h) resulted in the expected biphasic LH response, with an initial rapid release of LH during the first hour of infusion, followed by a second phase release during the subsequent 3 h. When verapamil (5 mg/h) was infused together with GnRH over a 4 h period, a significant decline of the rapid as well as delayed release of pituitary LH occurred. During the calcium antagonist infusion FSH release was also inhibited, indicating that Ca2+ is also important for the release of this hormone. Our data demonstrate that Ca2+ plays an essential role in the mechanism of GnRH action on both phases of LH release and the release of FSH in normal subjects.