Mice are insensitive to the antitesticular effects of luteinizing hormone-releasing hormone agonists.
Treatment of male rats with [(imBzl)-D-His6, Pro9-NEt]LHRH or [D-Trp6,Pro9-NEt]LHRH, potent agonists of LHRH, led to a marked decrease in serum testosterone levels and a reduction in testicular LH receptor concentration. Similar treatment of mice showed that they were resistant to the antitesticular effects of the LHRH agonists. To further explore the differences between rats and mice, the direct antitesticular effects of these peptides were investigated in hypophysectomized animals. Hypophysectomized rats and mice were given ovine FSH (50 micrograms), with or without a LHRH agonist (10 micrograms), daily for 5 days. On day 6, the testicular steroidogenic response to hCG was studied. In these studies the in vivo as well as the in vitro steroidogenic response of rat testes to hCG were inhibited by the LHRH analogs. In contrast, pretreatment of mice with the LHRH analogs did not affect their testicular steroidogenic response. Binding studies with the [125I]LHRH analog demonstrated receptors for this peptide on Leydig cells from adult rats. Receptors for LHRH were not, however, detectable on murine Leydig cells. These results suggest that one of the reasons for the lack of an antitesticular effect of LHRH agonists in mice may be due to the inability of these peptides to have a direct effect on testes and may relate to a lack of LHRH receptors.
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007016:Hypophysectomy; D007985:Leydig Cells / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011966:Receptors, LHRH; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*
D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C019176:Tryptal; D007986:Luteinizing Hormone; C029256:histrelin