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

Toxicol Lett. 2014 Apr 7;226(1):14-9. doi: 10.1016/j.toxlet.2014.01.022. Epub 2014 Jan 26.

Abstract

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 IC₆₀ 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.

Keywords: 3β-Hydroxysteroid dehydrogenase; Rat Leydig cells; Resveratrol; Steroidogenesis; Steroidogenic enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Enzyme Inhibitors / toxicity*
  • Humans
  • Leydig Cells / drug effects*
  • Leydig Cells / enzymology
  • Luteinizing Hormone / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stilbenes / toxicity*
  • Testosterone / biosynthesis*
  • Testosterone / blood

Substances

  • Endocrine Disruptors
  • Enzyme Inhibitors
  • Stilbenes
  • Testosterone
  • Luteinizing Hormone
  • 3-Hydroxysteroid Dehydrogenases
  • Resveratrol