Mevastatin inhibits ovarian theca-interstitial cell proliferation and steroidogenesis.
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.


METHODS
In vitro study.


METHODS
Academic laboratory.


METHODS
None.


METHODS
Effects of mevastatin on cultured theca-interstitial cells.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Daniel
D
Izquierdo
Nastaran
N
Foyouzi
Jakub
J
Kwintkiewicz
Antoni J
AJ
Duleba
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000096:biosynthesis*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013799:Theca Cells / Q000166:cytology* / Q000378:metabolism*
D006727:Hormone Antagonists; D006728:Hormones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C012258:mevastatin; D013739:Testosterone; D011374:Progesterone; D008148:Lovastatin