Comparison of effects of different statins on growth and steroidogenesis of rat ovarian theca-interstitial cells

Anna Sokalska, Scott D Stanley, Jesus A. Villanueva, Israel Ortega, Antoni J. Duleba

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of the cellular production of cholesterol and other products of the mevalonate pathway. Statins exert hepatic and extrahepatic effects, modulating the function of various tissues and organs, including ovaries. Previously, we have demonstrated that simvastatin inhibited cellular proliferation and reduced androgen production by ovarian theca-interstitial cells. The above actions are of translational relevance to the most common endocrine disorder among women in reproductive age: polycystic ovary syndrome. However, different statins may have distinctly different profiles of effects on cholesterol and androgens. The present study was designed to compare the effects of several statins on growth and steroidogenesis of rat theca-interstitial cells. The cells were incubated in the absence (control) or in the presence of simvastatin, lovastatin, atorvastatin, or pravastatin. Assessment of effects of statins on cell growth was carried out by evaluation of DNA synthesis and by estimation of the number of viable cells. Effects on steroidogenesis were evaluated by quantification of steroid production and expression of mRNA for the key enzyme regulating androgen production: Cyp17a1. Among tested statins, simvastatin exerted the greatest inhibitory effects on all tested parameters. The rank order of the effects of the tested statins is as follows: simvastatin > lovastatin > atorvastatin ≥ pravastatin. While the lipophilicity is likely to play a major role in determining the ability of statins to act on nonhepatic cells, other factors unique to individual cell types are also likely to be relevant.

Original languageEnglish (US)
Article numberArticle 44
JournalBiology of Reproduction
Volume90
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Theca Cells
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Growth
Androgens
Pravastatin
Lovastatin
Cholesterol
Hydroxymethylglutaryl CoA Reductases
Mevalonic Acid
Polycystic Ovary Syndrome
Enzymes
Ovary
Cell Count
Steroids
Cell Proliferation
Messenger RNA
Liver
DNA

Keywords

  • Cyp17a1
  • Ovarian theca-interstitial cells
  • Proliferation
  • Statins
  • Steroidogenesis

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Comparison of effects of different statins on growth and steroidogenesis of rat ovarian theca-interstitial cells. / Sokalska, Anna; Stanley, Scott D; Villanueva, Jesus A.; Ortega, Israel; Duleba, Antoni J.

In: Biology of Reproduction, Vol. 90, No. 2, Article 44, 2014.

Research output: Contribution to journalArticle

Sokalska, Anna ; Stanley, Scott D ; Villanueva, Jesus A. ; Ortega, Israel ; Duleba, Antoni J. / Comparison of effects of different statins on growth and steroidogenesis of rat ovarian theca-interstitial cells. In: Biology of Reproduction. 2014 ; Vol. 90, No. 2.
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