Effect of rifampicin on the biosynthesis of testosterone in rat testis

Male Wistar rats were treated with rifampicin (10 mg/kg) daily for 5 days. After 6 days, the rats were killed and the testes homogenised in tris buffer. The microsomal fractions were incubated with [4-14C]4-progesterone, [4-14C]17-hydroxyprogesterone or [4-14C]-androstene-3, 17-dione, respectively, and a NADPH generating system. In rifampicin-treated animals, less [4-14C]progesterone was recovered after incubation with testicular microsomes than in controls. There was no significant difference in the formation of 17-hydroxyprogesterone between rifampicin-treated animals and the controls; however, a significant increase was found in the androstenedione fraction (+83%) and the testosterone fraction (+48%) under the influence of rifampicin. When [4-14C]17-hydroxyprogesterone or [4-14C]4-androstene-3, 17-dione were incubated, no differences in the metabolic pattern were observed between treated and untreated rats. These findings suggest that rifampicin stimulates the activity of 17 alpha-hydroxylase in the microsomal fraction of rat testes, thus leading to an increased formation of testosterone and androstenedione; in contrast, the 17, 20-lyase and 17 beta-hydroxysteroid-dehydrogenase remain unaffected by rifampicin.