THE ROLE OF CYCLIC-AMP PRODUCTION, CALCIUM-CHANNEL ACTIVATION AND ENZYME-ACTIVITIES IN THE INHIBITION OF TESTOSTERONE SECRETION BY AMPHETAMINE

1 The aim of this study was to investigate the mechanism by which amph etamine exerts its inhibitory effect on testicular interstitial cells of male rats. 2 Administration of amphetamine (10(-12)-10(-6) M) in vi tro resulted in a dose-dependent inhibition of both basal and human ch orionic gonadotropin (hCG, 0.05 iu ml(-1))-stimulated release of testo sterone. 3 Amphetamine (10(-9) M) enhanced the basal and hCG-increased levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulat ion in vitro (P<0.05) in rat testicular interstitial cells. 4 Administ ration of SQ22536, an adenylyl cyclase inhibitor, decreased the basal release (P<0.05) of testosterone in vitro and abolished the inhibitory effect of amphetamine. 5 Nifedipine (10(-6) M) alone decreased the se cretion of testosterone (P<0.01) but it failed to modify the inhibitor y action of amphetamine (10(-10)-10(-6) M). 6 Amphetamine (10(-10)-10( -6) M) significantly (P<0.05 or P<0.01) decreased the activities of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), P450c17, and 17-ketost eroid reductase (17-KSR) as indicated by thin-layer chromatography. (t .l.c.). 7 These results suggest that increased cyclic AMP production, decreased Ca2+ channel activity and decreased activities of 3 beta-HSD , P450c17, and 17-KSR are involved in the inhibition of testosterone p roduction induced by the administration of amphetamine.