Inhibition of aldosterone production by testosterone in male rats

In vivo and in vitro experiments were designed to assess the effect of testosterone on aldosterone secretion in male rats. Orchidectomized rats were injected subcutaneously with oil or testosterone propionate ([TP] 2 mg/kg) for 7 days. Intact rats were injected with oil only. The results indicate that the plasma aldosterone level was higher in orchidectomized versus intact and TP-replaced rats. In the in vitro study, testosterone caused a marked decrease of aldosterone secretion by zona glomerulosa (ZG) cells, but failed to alter the accumulation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP). Testosterone significantly decreased the corticotropin (ACTH)-stimulated production of aldosterone and accumulation of cAMP in rat ZG cells. The conversion of corticosterone to aldosterone and of 25-OH-cholesterol to pregnenolone, as well as angiotensin II (ANG II)-stimulated production of aldosterone, were decreased by testosterone. These results suggest that testosterone inhibits the basal and ANG II- and ACTH-stimulated release of aldosterone, via inhibition of aldosterone synthase activity and cytochrome P-450 side-chain cleavage (P450scc) activity, and ACTH-stimulated cAMP accumulation in rat ZG cells.