OBJECTIVE: Statins reduce cardiovascular risks by improving hypercholesterolemia, reducing vascular smooth muscle proliferation, and ameliorating inflammation. Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risks and is characterized by ovarian theca-interstitial hyperplasia and hyperandrogenism. This study tested the hypothesis that mevastatin limits theca-interstitial proliferation and decreases steroidogenesis. DESIGN: In vitro study. SETTING: Academic laboratory. PATIENT(S): None. INTERVENTION(S): Effects of mevastatin on cultured theca-interstitial cells. MAIN OUTCOME MEASURE(S): Proliferation was evaluated by determination of DNA synthesis using thymidine incorporation assay and by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay. Production of P and T was determined by specific radioimmunoassays. RESULT(S): Mevastatin induced a profound concentration-dependent inhibition of DNA synthesis. At the highest concentration (30 microM), mevastatin inhibited DNA synthesis by 92%. Similarly, in the MTT proliferation assay, mevastatin induced a concentration-dependent decrease in cell number. Mevastatin decreased production of P (by up to 49%) and T (by up to 52%); these effects remained significant when the effect on cell culture protein content was accounted for. CONCLUSION(S): Mevastatin inhibits proliferation of theca-interstitial cells; it also inhibits P and T production independently of the effects on cell growth. These findings provide a foundation for studies evaluating statins as potential therapeutic agents in the treatment of ovarian mesenchymal hyperplasia and hyperandrogenism characteristic of PCOS.
OBJECTIVE: Statins reduce cardiovascular risks by improving hypercholesterolemia, reducing vascular smooth muscle proliferation, and ameliorating inflammation. Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risks and is characterized by ovarian theca-interstitial hyperplasia and hyperandrogenism. This study tested the hypothesis that mevastatin limits theca-interstitial proliferation and decreases steroidogenesis. DESIGN: In vitro study. SETTING: Academic laboratory. PATIENT(S): None. INTERVENTION(S): Effects of mevastatin on cultured theca-interstitial cells. MAIN OUTCOME MEASURE(S): Proliferation was evaluated by determination of DNA synthesis using thymidine incorporation assay and by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay. Production of P and T was determined by specific radioimmunoassays. RESULT(S): Mevastatin induced a profound concentration-dependent inhibition of DNA synthesis. At the highest concentration (30 microM), mevastatin inhibited DNA synthesis by 92%. Similarly, in the MTT proliferation assay, mevastatin induced a concentration-dependent decrease in cell number. Mevastatin decreased production of P (by up to 49%) and T (by up to 52%); these effects remained significant when the effect on cell culture protein content was accounted for. CONCLUSION(S): Mevastatin inhibits proliferation of theca-interstitial cells; it also inhibits P and T production independently of the effects on cell growth. These findings provide a foundation for studies evaluating statins as potential therapeutic agents in the treatment of ovarian mesenchymal hyperplasia and hyperandrogenism characteristic of PCOS.
Authors: Selma F Witchel; Sergio E Recabarren; Frank González; Evanthia Diamanti-Kandarakis; Kai I Cheang; Antoni J Duleba; Richard S Legro; Roy Homburg; Renato Pasquali; Rogerio A Lobo; Christos C Zouboulis; Fahrettin Kelestimur; Franca Fruzzetti; Walter Futterweit; Robert J Norman; David H Abbott Journal: Endocrine Date: 2012-06-04 Impact factor: 3.633
Authors: Israel Ortega; Amanda B Cress; Donna H Wong; Jesus A Villanueva; Anna Sokalska; Ben C Moeller; Scott D Stanley; Antoni J Duleba Journal: Biol Reprod Date: 2012-01-30 Impact factor: 4.285
Authors: Izabela J Rzepczynska; Piotr C Piotrowski; Donna H Wong; Amanda B Cress; Jesus Villanueva; Antoni J Duleba Journal: Biol Reprod Date: 2009-07-01 Impact factor: 4.285