CALCIUM-ANTAGONISTS AND HORMONE-RELEASE .3. ROLE OF CALCIUM IN THE BIPHASIC RELEASE OF LUTEINIZING-HORMONE IN RESPONSE TO GONADOTROPIN-RELEASING HORMONE INVIVO

Recent in vitro studies have demonstrated that Ca2+ plays an essential role in gonadotrophin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. Verapamil, a substance known to inhibit Ca entry into cells, is capable of inhibiting basal gonadotropin release as well as the release of LH and FSH in response to an i.v. bolus of GnRH. The effects of Ca antagonists on the 2 phases of pituitary LH release in response to constant GnRH infusion in normal subjects were examined. In 6 men, constant infusion of GnRH (0.2 .mu.g/min .times. 4 h) resulted in the expected biphasic LH response, with an initial rapid release of LH during the 1st h of infusion, followed by a 2nd phase release during the subsequent 3 h. When verapmil (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 Ca antagonist infusion FSH release was also inhibited, indicating that Ca2+ is also important for the release of this hormone. 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.