DIRECT INHIBITORY EFFECT OF GnRH ON ANDROGEN SECRETION BY OVARIAN INTERSTITIAL CELLS1

Abstract

GnRH [gonadotropin-releasing hormone] and a potent GnRH agonist [des-Gly10,D-Leu6,(N.alpha.Me)Leu7,Pro9-NHEt-GnRH] inhibit basal and luteinizing hormone stimulated rat ovarian androgen biosynthesis in vitro. The inhibitory effects of GnRH are dose-dependent and completely inhibited by concomitant treatment with a GnRH antagonist [D-pGlu'',D-Phe2,D-Trp3,6-GnRH]. The GnRH action is very rapid (t1/2 [half-life] = 10 min) and persists after thorough washing of the cells. Apparently GnRH acts at a stereospecific binding site on ovarian theca and/or interstitial cells (probably the theca cells) to rapidly and perhaps irreversibly inhibit androgen biosynthesis.