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Horm Metab Res 2011; 43(4): 250-256
DOI: 10.1055/s-0030-1270525
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Rosiglitazone and Pioglitazone Inhibit Estrogen Synthesis in Human Granulosa Cells by Interfering with Androgen Binding to Aromatase

D. Seto-Young1 , D. Avtanski1 , G. Parikh1 , P. Suwandhi1 , M. Strizhevsky1 , T. Araki1 , Z. Rosenwaks2 , L. Poretsky1
  • 1G. J. Friedman Diabetes Institute and the Division of Endocrinology, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, USA
  • 2The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, USA
Further Information

Publication History

received 13.10.2010

accepted 20.12.2010

Publication Date:
14 February 2011 (online)

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Abstract

The effects of rosiglitazone or pioglitazone (thiazolidinediones, TZDs) on estrogen production and aromatase activity in human ovarian cells were examined. Human granulosa cells were incubated in the tissue culture medium supplemented with androstenedione or testosterone, with or without insulin, TZDs, or type 1 17β-hydroxysteroid-dehydrogenase (17β-HSD) inhibitor. Estrogen concentrations in the conditioned medium, aromatase mRNA and protein expression in the cells and androgen substrate binding to aromatase were measured. With androstenedione as substrate, rosiglitazone or pioglitazone inhibited estrone production by up to 22% (p<0.012) while type 1 17β-HSD inhibitor enhanced this effect of rosiglitazone or pioglitazone by 37% (p<0.001) and by 67% (p<0.001), respectively. With testosterone as substrate, rosiglitazone or pioglitazone inhibited estradiol production by 32% (p<0.001). With 3H-testosterone as substrate, rosiglitazone or pioglitazone inhibited the 3H-tritiated water release by the cultured cells by 45% and 35%, respectively, thus directly demonstrating inhibition of aromatase. Rosiglitazone or pioglitazone, however, had no significant effect on aromatase mRNA or protein expression. Rosiglitazone or pioglitazone inhibited 125I-androstenedione and 125I-testosterone binding to aromatase by 38% (p<0.001). It was concluded that rosiglitazone or pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase.

Key words

thiazolidinediones - estrogens - aromatase - insulin sensitivity - PPAR-γ - polycystic ovary syndrome

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Correspondence

D. Seto-YoungPhD 
L. PoretskyMD 

Division of Endocrinology

Beth Israel Medical Center

317 East 17 th Street

Fierman Hall,7 th Floor

NY 10003

New York

USA

Phone: +1/212/420 4666

Fax: +1/212/420 2224

Email: dyoung@chpnet.org

Email: lporetsk@chpnet.org

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