1. The aim of this study was to investigate the mechanism by which amphetamine exerts its inhibitory effect on testicular interstitial cells of male rats. 2. Administration of amphetamine (10-12-10-6 M) in vitro resulted in a dose-dependent inhibition of both basal and human chorionic gonadotropin (hCG, 0.05 iu ml-1)-stimulated release of testosterone. 3. Amphetamine (10-9 M) enhanced the basal and hCG-increased levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in vitro (P < 0.05) in rat testicular interstitial cells. 4. Administration 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 secretion of testosterone (P < 0.01) but it failed to modify the inhibitory 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 3β-hydroxysteroid dehydrogenase (3β-HSD), P450c17, and 17-ketosteroid 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 3β-HSD, P450c17, and 17-KSR are involved in the inhibition of testosterone production induced by the administration of amphetamine.
- Cyclic AMP
ASJC Scopus subject areas