Disrupting androgen production of Leydig cells by resveratrol via direct inhibition of human and rat 3β-hydroxysteroid dehydrogenase

• Resveratrol inhibits androgen production in rat Leydig cells.
• Resveratrol inhibits rat and human 3β-HSD activities.
• Resveratrol is a competitive inhibitor of 3β-HSD.

Resveratrol is a polyphenol produced by several plants. It has been demonstrated that it has anti-inflammatory, antitumor, and anti-diabetic effects in animal models. However, its side effects are generally unclear. In the present study, we reported that resveratrol inhibited luteinizing hormone-stimulated androgen production in rat immature Leydig cells. Further analysis demonstrated that it was a competitive inhibitor of rat and human 3β-hydroxysteroid dehydrogenase with IC50 values of 3.87 ± 0.06 and 8.48 ± 0.04 μM, respectively. The inhibition on 3β-hydroxysteroid dehydrogenase was specific since it did not inhibit another hydroxysteroid dehydrogenase 17β-hydroxysteroid dehydrogenase 3 at the highest concentration (100 μM) tested. In conclusion, resveratrol potentially interferes with androgen biosynthesis of rat Leydig cells.