Direct effects of propylthiouracil on testosterone secretion in rat testicular interstitial cells

The aim of this study was to investigate the mechanism by which propylthiouracil (PTU) exerts its inhibitory effects on the production of testosterone by rat testicular interstitial cells. The plasma testosterone concentration was decreased 60 and 120 min after an intravenous infusion of PTU (10 or 20 mg kg(-1)), but the concentration of plasma T(4) was unaffected by the drug treatment. Exposure of anterior pituitary tissue to PTU (3-12 mM) in vitro did not affect either basal or gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. PTU (3 - 12 mM) inhibited both the basal and the human chorionic gonadotropin (hCG, 0.05 i.u. ml(-1))-stimulated release of testosterone from rat testicular tissue in vitro; at the highest concentration tested (12 mM), it also inhibited the forskolin or 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cyclic AMP)-stimulated release of testosterone. The 25-OH-cholesterol (10(-7)-10(-5) M)-stimulated release of pregnenolone and testosterone by the testicular interstitial cells was inhibited by PTU (12 mM, P<0.05). The results suggest that the inhibitory actions of PTU on testosterone secretion are exerted, at least in part, at the testicular level through a mechanism which is independent of thyroid status and which involves a reduction in P450scc activity and, hence, in the conversion of cholesterol to pregnenolone.