LH-RH antagonist inhibits gonadal steroid secretion in vitro.
This investigation was aimed at studying the direct action of LH-RH derivatives on gonadal function. Modulation by LH-RH antagonist (Ac-[D-beta-Nal1, D-p-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10]-LH-RH) and agonist of LH-RH (D-Ser(TBU)6, AzaGly10-LH-RH) and native LH-RH of HCG-stimulated steroidogenesis in testicular Leydig cells and luteal cells was studied in vitro. The LH-RH antagonist (3.2 X 10(-8) M) was found to change ED50 of HCG from 2 X 10(-11) M to 5.5 X 10(-11) M in the Leydig cell culture system. In addition, the antagonist was noted to override the stimulatory action of native LH-RH in Leydig cells. Furthermore, the agonist was found to augment HCG-provoked testosterone secretion. Similarly, the LH-RH antagonist at 10(-9) M blunted HCG-stimulated progesterone secretion in the luteal cell culture system and increased the ED50 of HCG from 8.7 X 10(-13) to 7.7 X 10(-12) M. In contrast to the Leydig cell culture system native LH-RH (10(-8) M) and the agonist (10(-8) M) increased the ED50 of HCG in luteal cells from 8.7 X 10(-13) M to 3 X 10(-12) M and 2.3 X 10(-12) M, respectively. Present data combine to suggest that LH-RH antagonists act at least partially at the gonadal level and may be clinically useful to inhibit Leydig cell and ovarian function.
D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone