Statins inhibit growth of human theca-interstitial cells in PCOS and non-PCOS tissues independently of cholesterol availability.
BACKGROUND
Polycystic ovary syndrome (PCOS) is associated with ovarian enlargement, prominent theca-interstitial hyperplasia, and excessive androgen production. Recent clinical trials have demonstrated that statins, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, decrease androgen levels in women with PCOS.


OBJECTIVE
The present study evaluated the effect of statins on proliferation of human ovarian theca-interstitial cells.


METHODS
In vitro experiments were performed in the university research laboratory.


METHODS
Human theca-interstitial cells were isolated from ovaries of PCOS (n=4) and non-PCOS (n=4) patients.


METHODS
The cells were incubated for 48 h without additives (control) or with simvastatin (3-30 μm), mevastatin (3-30 μm), and/or the cell- and mitochondrion-permeable form of cholesterol (22-hydroxycholesterol; 10 μm). To determine whether the effects of statins could be affected by leukocytes, the experiment was carried out on cells not purified of leukocytes and cells purified using anti-CD-45 immunomagnetic beads. The effect of statins on proliferation was evaluated by determination of DNA synthesis using radiolabeled thymidine-incorporation assay and by quantification of viable cells using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenil)-2H-tetrazolium assay.


RESULTS
Statins induced an inhibition of DNA synthesis in both the absence and the presence of 22-hydroxycholesterol; furthermore, 22-hydroxycholesterol alone also inhibited DNA synthesis. These effects of statins and 22-hydroxycholesterol were confirmed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenil)-2H-tetrazolium assay. Comparable inhibition of proliferation was observed in cells obtained from women with and without PCOS and in cell preparations treated and not treated with anti-CD-45 immunomagnetic beads.


CONCLUSIONS
Statins inhibit proliferation of human theca-interstitial cells irrespective of the availability of cholesterol and independently of leukocytes both in normal and PCOS ovaries.
Sokalska
Anna
A
Department of Obstetrics and Gynecology, University of California Davis, 4860 Y Street, Sacramento, California 95817, USA.
Piotrowski
Piotr C
PC
Rzepczynska
Izabela J
IJ
Cress
Amanda
A
Duleba
Antoni J
AJ
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007633:Keratins / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D017697:Premenopause; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013799:Theca Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014746:Vimentin; D007633:Keratins; D005169:Factor VIII; D002784:Cholesterol; D019821:Simvastatin; D013936:Thymidine
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