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Anna Sokalska, Piotr C. Piotrowski, Izabela J. Rzepczynska, Amanda Cress, Antoni J. Duleba, Statins Inhibit Growth of Human Theca-Interstitial Cells in PCOS and Non-PCOS Tissues Independently of Cholesterol Availability, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 12, 1 December 2010, Pages 5390–5394, https://doi.org/10.1210/jc.2010-0770
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Context: 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.
Design and Settings:In vitro experiments were performed in the university research laboratory.
Patients: Human theca-interstitial cells were isolated from ovaries of PCOS (n = 4) and non-PCOS (n = 4) patients.
Main Outcome Measures: 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.
