Human choriogonadotropin-induced desensitization of granulosa-cell adenylate cyclase to gonadotropins and loss of LH/hCG receptor.

Immature female rats that had been primed with pregnant-mare serum gonadotropin (PMSG) were injected intravenously with various doses of human choriogonadotropin (hCG) for the investigation of the relationship between adenylate cyclase activities and the concentrations of LH/hCG receptor in luteinizing granulosa cells. Injection of 1 microgram of hCG induced a loss of LH and FSH sensitivities of adenylate cyclase within 6 h and a disappearance of free LH/hCG receptors within 24 h. Basal adenylate cyclase activity has a transient maximum at 6 h after hCG injection. After injection of 100 micrograms of hCG the loss of LH sensitivity of adenylate cyclase and free LH/hCG receptors occurred immediately, but the changes in FSH-stimulated and basal activities followed the same time scale as after injection of 1 microgram of hCG. When hCG was omitted from the injections the response of the animals to the endogenous gonadotropin surge varied. A complete desensitization of adenylate cyclase to LH and FSH stimulation and a 65% loss of free LH/hCG receptors were found at 24 h if the follicles were ovulated. These results suggest that occupation of a limited number of LH/hCG receptors in granulosa cells induces adenylate cyclase refractory to further stimulation by gonadotropins. The transient elevation of basal adenylate cyclase activity and its desensitization to further stimulation by gonadotropins may have a role in physiological processes leading to ovulation and luteinization.