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.