Document Detail


Statins inhibit growth of human theca-interstitial cells in PCOS and non-PCOS tissues independently of cholesterol availability.
MedLine Citation:
PMID:  20826585     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anna Sokalska; Piotr C Piotrowski; Izabela J Rzepczynska; Amanda Cress; Antoni J Duleba
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-08
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-01-14     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5390-4     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Cell Division / drug effects
Cell Survival / drug effects
Cholesterol / metabolism*
Factor VIII / metabolism
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*,  therapeutic use
Keratins / metabolism
Polycystic Ovary Syndrome / drug therapy,  metabolism,  pathology*,  surgery
Premenopause
Simvastatin / pharmacology*,  therapeutic use
Theca Cells / cytology,  drug effects*,  pathology
Thymidine / metabolism
Vimentin / metabolism
Grant Support
ID/Acronym/Agency:
R01 HD050656/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Vimentin; 68238-35-7/Keratins; 9001-27-8/Factor VIII; 97C5T2UQ7J/Cholesterol; AGG2FN16EV/Simvastatin; VC2W18DGKR/Thymidine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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