Direct effects of propylthiouracil on testosterone production in monkeys

Propylthiouracil (PTU) is an anti-thyroid drug. However, the direct effects of PTU on the endocrine functions of non-thyroid glands are unclear. In the present study, we examined the acute effects of PTU on testosterone secretion in monkeys. Male monkeys were infused intravenously with PTU for 30 min. Blood samples were collected at several time intervals. Monkey testicular interstitial cells were cultured with PTU, human chorionic gonadotropin (hCG), or forskolin, at 34 degrees C for 1 h. In another study, steroidogenesis in monkey testicular interstitial cells were examined. PTU decreased plasma testosterone but not plasma thyroxine (T4) and luteinizing hormone (LH) levels in monkeys. Administration of PTU resulted in a dose-dependent inhibition of basal and hCG-, as well as forskolin-stimulated testosterone release by monkey testicular interstitial cells. PTU also diminished the stimulatory effects induced by androstenedione. These results suggest that PTU inhibits testosterone secretion via a mechanism independent of the secretion of T4 and LH in primates. The inhibitory mechanism of PTU on testosterone production involves a decreased activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and post-cAMP pathways.