Receptors and inhibitory actions of gonadotropin-releasing hormone in the fetal Leydig cell.
The receptors and actions of gonadotropin-releasing hormone (GnRH) were analyzed in cultured testicular cells from 20.5-day fetal rats, in which treatment with luteinizing hormone (LH) maintained Leydig cell steroidogenesis and gonadotropic responses for up to 2 weeks. Testicular GnRH receptors were present on the 5th postnatal day, but were not demonstrable in fetal testes or 2-day cultures thereof. However, GnRH receptors were readily detectable in 4-day cultured fetal testes and were increased by exposure to GnRH agonists. In LH-treated cultures, GnRH sites were reduced by about 50% and did not increase during incubation with GnRH agonists. In such cultures, GnRH agonists inhibited LH-dependent steroid production and abolished the acute testosterone response to human chorionic gonadotropin. The half-maximal inhibitory concentration of [D-Ala6]des-Gly10-GnRH-N-ethylamide (3 X 10(-10)M) was commensurate with its binding affinity for testis receptors (Kd = 1.4 X 10(-10)M). In contrast, GnRH agonists had no inhibitory effects in 2-day cultures prior to the detection of GnRH receptors. The expression of functional GnRH receptors during culture in the absence of gonadotropin and their suppression in LH-treated cultures suggest that pituitary gonadotropins exert a tonic inhibitory effect upon testicular GnRH receptors. The demonstrated inhibitory actions of GnRH on steroidogenesis, with the expression of GnRH receptors in cultured fetal testes and 5-day postnatal testes, indicate that GnRH agonists could influence the actions of gonadotropins upon Leydig cell function in the neonatal testis.
D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D005333:Fetus; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D011247:Pregnancy; D051381:Rats; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D011966:Receptors, LHRH; D013737:Testis / Q000196:embryology; D013739:Testosterone / Q000378:metabolism
D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone