Direct inhibition of rat leydig cell function by tamoxifen.
The effects of tamoxifen on rat testicular steroidogenesis were studied using dispersed interstitial cells. Tamoxifen significantly inhibited LH-, and 8-bromo-adenosine 3',5'-monophosphate (8-bromo-cyclic AMP)-stimulated testosterone synthesis in a dose-dependent manner. Tamoxifen (10(-5)M) also reduced LH-stimulated cyclic AMP formation. The addition of equimolar concentrations of 17 beta-estradiol or tamoxifen separately to interstitial cells resulted in similar inhibition of LH-stimulated testosterone synthesis. When equimolar concentrations of 17 beta-estradiol and tamoxifen were added concomitantly to interstitial cells, the inhibition was additive. Present studies demonstrate that tamoxifen has direct inhibitory effects on testicular steroidogenesis: both at the plasma membrane resulting in decreased cyclic AMP formation and also at steps subsequent to cyclic AMP.
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007985:Leydig Cells / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood
D013629:Tamoxifen; D013739:Testosterone; D007986:Luteinizing Hormone; D000242:Cyclic AMP