THE INHIBITORY-ACTION OF TAXOL ON GRANULOSA-CELL STEROIDOGENESIS IS REVERSIBLE

Taxol is a novel anticancer agent extracted from the bark of Pacific y ew trees. The drug has been approved by the FDA for the treatment of a dvanced ovarian cancer and is in clinical trials for other malignancie s, including breast cancer. The goals of this study were to determine whether taxol adversely and irreversibly affects ovarian granulosa cel l steroidogenesis. Cultured porcine granulosa cells were treated with taxol (0.12-12 mu M) or vehicle (0.01-1% ethanol) in the absence or pr esence of 10(-9) M hCG in a time- and dose-response study. Morphologic al changes were recorded every 2 h, and media were collected for the m easurement of progesterone (P-4) and 17 beta-estradiol. Taxol suppress ed both basal P-4 and 17 beta-estradiol production and hCG-stimulated P-4 production in a time- and dose-dependent manner and drastically ch anged cell shape by causing disorganization of microtubule bundles and other subcellular organelles. hCG partially reversed the steroid inhi bition induced by taxol. These changes are not attributed to ethanol u sed as the vehicle, because ethanol at higher concentrations than that present in taxol did not suppress P-4 production. When taxol was remo ved from the culture, P-4 production returned to control levels. The r esults of this study show that taxol causes a significant, but reversi ble, inhibition of granulosa cell steroidogenesis. This inhibitory eff ect can be partially overcome by cotreatment with hCG.