Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cells steroidogenesis

Israel Ortega, Jesus A. Villanueva, Donna H. Wong, Amanda B. Cress, Anna Sokalska, Scott D. Stanley, Antoni J. Duleba

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Background: Polycystic ovary syndrome (PCOS) is characterized by ovarian enlargement, hyperplastic theca compartment and increased androgen production due to, at least in part, excessive expression of several key genes involved in steroidogenesis. Previously, our group has demonstrated that simvastatin, competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a rate-limiting step of the mevalonate pathway, reduces rat-theca interstitial cell steroidogenesis by inhibiting Cyp17a1 gene expression, the key enzyme of the androgen biosynthesis pathway. Recently, we demonstrated that resveratrol, a bioflavonoid abundant in red grapes, decreases rat theca-interstitial cell steroidogenesis and this suppressive effect is mediated through mechanisms independent of the mevalonate pathway. The present study evaluated the effect of combining simvastatin and resveratrol treatments on rat theca-interstitial cell steroidogenesis. Methods. Rat theca-interstitial cells isolated from 30 day-old female rats were cultured for up to 48 h with or without simvastatin (1 μM) and/or resveratrol (3-10 μM). Steroidogenic enzymes gene expression was evaluated by quantitative real time PCR and steroid levels were measured by liquid chromatography-mass spectrometry. Comparisons between groups were performed using ANOVA and Tukey test. Results: Resveratrol potentiated inhibitory effects of simvastatin on androstenedione and androsterone production in theca-interstitial cells. This suppressive effect correlated with profound inhibition in Cyp17a1 mRNA expression in the presence of a combination of resveratrol and simvastatin. Conclusions: The present findings indicate that resveratrol potentiates the simvastatin-induced inhibitory effect on theca-interstitial cell androgen production, raising the possibility of development of novel treatments of PCOS.

Original languageEnglish
Article number21
JournalJournal of Ovarian Research
Issue number1
StatePublished - Feb 13 2014

Bibliographical note

Funding Information:
This study was supported by grant R01-HD050656 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (to AJD).


  • Androgens
  • CYP17A1
  • Ovarian theca-interstitial cells
  • Resveratrol
  • Simvastatin
  • Steroidogenesis

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology


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