title: The role of cyclic AMP production, calcium channel activation and enzyme activities in the inhibition of testosterone secretion by amphetamine.
abstract: 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 3beta-hydroxysteroid dehydrogenase (3beta-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 3beta-HSD, P450c17, and 17-KSR are involved in the inhibition of testosterone production induced by the administration of amphetamine.
authors.affiliation: Department and Graduate Institute of Physiology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: S C
authors.initials: SC
authors.lastname: Tsai
authors.forename: J J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Y C
authors.initials: YC
authors.lastname: Chiao
authors.forename: C C
authors.initials: CC
authors.lastname: Lu
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: J Y
authors.initials: JY
authors.lastname: Yeh
authors.forename: M J
authors.initials: MJ
authors.lastname: Lo
authors.forename: M M
authors.initials: MM
authors.lastname: Kau
authors.forename: S W
authors.initials: SW
authors.lastname: Wang
authors.forename: P S
authors.initials: PS
authors.lastname: Wang
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006063:Chorionic Gonadotropin; C017759:9-(tetrahydro-2-furyl)-adenine; D013739:Testosterone; D000661:Amphetamine; D000242:Cyclic AMP; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D009543:Nifedipine; D000225:Adenine