Troglitazone: a possible modulator of ovarian steroidogenesis.
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.


CONCLUSIONS
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 steroidogenesis.
Mitwally
Mohamed F M
MF
Reproductive Sciences Division, Department of Obstetrics and Gynecology, University of Toronto, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
Witchel
Selma F
SF
Casper
Robert F
RF
D000328:Adult; D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007016:Hypophysectomy; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D013256:Steroids / Q000096:biosynthesis*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D000728:Androgens; D000975:Antioxidants; D006063:Chorionic Gonadotropin; D002839:Chromans; D013256:Steroids; D013844:Thiazoles; D045162:Thiazolidinediones; D011374:Progesterone; D000077288:Troglitazone