Gonadotropin-induced regulation of luteinizing hormone receptors and desensitization of testicular 3':5'-cyclic AMP and testosterone responses.
Administration of human chorionic gonadotropin (hCG) to male rats was followed by dose-related changes in luteinizing hormone (LH) receptors in the testis. After treatment with a low dose of hCG (10international units), the number of LH receptors increased slightly over the first 24 hr, then fell to about 30% of the control value. These changes occurred with occupancy of only 8% of the available receptors, and were initially accompanied by increased basal testosterone production in vitro with no change in basal 3'5'-cyclic AMP production. During stimulation with hCG in vitro, such testes showed a transient decrease in cyclic AMP response on the first day after gonadotropin treatment and no change in testosterone response. By contrast, a 20-fold higher dose of hCG caused more rapid and complete loss of LH receptors, with major and transient occupancy of receptors at 24 hr and marked elevations of basal cyclic AMP and testosterone production in vitro. The initial occupancy of receptors was accompanied by a rapid fall in the cyclic AMP response to hCG in vitro, and was followed by marked receptor loss and inhibition of the cyclic AMP response for up to 5 days. The testosterone response to hCG in vitro was completely inhibited for about 3 days, then rose to the control level at 5 days, when only a small proportion of the original receptor sites and cyclic AMP response had begun to return. Such complete recovery of the steroidogenic response when only a fraction of the receptor population had returned was consistent with the presence of receptor reserve or "spare" receptors in the testis. These studies have demonstrated that negative regulation of LH receptors by exogenous gonadotropin is accompanied by consequent changes in cyclic AMP and testosterone responses to hCG in vitro. Hormone induced desensitization of interstitial cell responses was initially related to occupancy of LH receptors and later to a protracted loss of receptor sites.
D000818:Animals; D006063:Chorionic Gonadotropin / Q000097:blood / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D013739:Testosterone; D007986:Luteinizing Hormone; D000242:Cyclic AMP