The mechanism of gonadotropin induced desensitization of rat ovarian adenylate cyclase in the cell free state and the role of GTP in this process.

Gonadotropin induced desensitization of adenylate cyclase (AC) in purified rat ovarian plasma membrane preparations requires a 40 min preincubation period with that same hormone and guanosine triphosphate (GTP). This phenomenon can be demonstrated for the response of AC to luteinizing hormone (LH), follicle stimulating hormone (FSH) and human chorionic gonadotropin (hCG), all of which display a strongly homologous rather than heterologous type of desensitization. In the desensitized state the enzyme retains its capacity to fully respond to stimulation by NaF. It is also shown that a possible basis for reduced responsiveness of AC to hormones in the desensitized state stems from the fact the hormone can bind but no longer accelerates the "GTP-regulatory cycle". Taken together these findings support the view, that the decreased ability of the hormone receptor in regulating AC activity in the desensitized state, results from a temporary change induced by the hormone in the receptor itself.