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 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 Ca 2+ 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.British Journal of Pharmacology (1997) 122 , 949–955; doi: 10.1038/sj.bjp.0701463