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Journal of the Society for Gynecologic Investigation
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Troglitazone: A Possible Modulator of Ovarian Steroidogenesis

Mohamed F. M. Mitwally, MD

Selma F. Witchel, MD

Reproductive Sciences Division, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada: Department of Gynecology and Obstetrics, State University of New York (SUNY) at Buffalo, Buffalo, New York; Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania

Robert F. Casper, MD

Reproductive Sciences Division, Department of Obstetrics & Gynecology, University of Toronto, Room 876, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada. rfcasper{at}aol.com

Objective: Troglitazone increases insulin sensitivity. When used to treat women with insulin-resistant polycystic ovary syndrome (PCOS), troglitazone lowers androgen concentrations and improves ovulatory, endocrine, and metabolic disturbances. However, it is not known whether these effects are due to increased peripheral insulin sensitivity only or to direct effects on steroidogenesis. To determine whether troglitazone has a direct effect on ovarian steroidogenesis, we studied the effect of troglitazone on androgen production in cultured rat theca interstitial cells (rTICs) and on progesterone production in cultured human granulosa lutein cells (hGLCs).

Methods: Primary cell cultures of rTICs were isolated from the ovaries of hypophysectomized immature Sprague-Dawley rats, and hGLCs was obtained from women who had in vitro fertilization-embryo transfer. Treatments included troglitazone, insulin, LH, hCG, and combinations of these agents. Media were collected and assayed for androsterone and progesterone.

Results: Troglitazone decreased both basal and insulin-, LH-, and hCG-stimulated androsterone production by TIC and progesterone production by hGLCs in a dose-dependent manner.

Conclusion: We found a direct effect of troglitazone on the production of androsterone by rTICs and progesterone by hGLCs. These results suggest that the beneficial effects of troglitazone in PCOS may not be due solely to improvement of peripheral insulin resistance and hyperinsulinemia, but also to a possible direct effect on ovarian steroidogensis.

Key Words: Troglitazone • steroidogenesis • androgen • progesterone • theca cells • granulosa cells • polycystic ovary syndrome

Journal of the Society for Gynecologic Investigation, Vol. 9, No. 3, 163-167 (2002)
DOI: 10.1177/107155760200900308
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