GLUTATHIONE-S-TRANSFERASE EXPRESSION IN THE MURINE OVARY

Abstract

Glutathione-S-Transferases (GST's) are a large family of enzymes which play a role in detoxification of xenobiotics by catalyzing the formation of glutathione conjugates. In addition, a number of studies have implicated a role for the GST family as regulators of signal transduction pathways, in particular mitogen-activated protein kinase (MAPK) pathways. 4-Vinylcyclohexane diepoxide (VCD) is an occupational chemical that destroys small pre-antral follicles in rodents. Previously, it has been shown that ovarian exposure to VCD resulted in increased activities of JNK and p38 MAPK. This study was designed to investigate whether one or more of the major GST classes might play a role in the VCD-induced ovotoxicity in mice. A post-natal day 4 (PND4) mouse whole ovary culture system (enriched in target small pre-antral follicles) was employed to examine expression of the major GST classes, alpha, mu, omega, pi, and theta, using Real-Time PCR. Comparison between the classes showed that GST alpha was expressed at the lowest level. Relative to GST alpha, GST omega, theta, mu and pi showed 12.9, 154, 201 and 352-fold greater expression, respectively. In addition, the effect of treatment with 15μM VCD for 15d in culture was examined. Expression of both GST pi and mu classes were increased (P<0.05) by 38% and 81%, respectively compared to control treatment. These findings demonstrate differential expression of the major GST classes in the ovary in response to xenobiotic exposure and suggest a potential role for GST pi and mu in ovarian biotransformation of VCD (Supported by ES09246 and Center grant 06694). (poster)