EFFECT OF OVARIECTOMY AND SEX-HORMONE REPLACEMENT ON GLUTATHIONE AND GLUTATHIONE-RELATED ENZYMES IN RAT HEPATOCARCINOGENESIS

The effects of ovariectomy and hormone replacement in control and carc inogen treated female rats were investigated by measuring whole blood and liver glutathione (WGSH, HGSH), glutathione S-transferase (GST), g lutathione peroxidase (GPx), and glutathione reductase (GRx) and histo logical evaluation. Hepatocarcinogenesis was induced by diethylnitrosa mine and 2-acetylaminofluorene. In control rats not receiving carcinog en, ovariectomy significantly increased the GST and GRx activities. Re placement with either estrogen or progesterone reduced the GST activit ies to below intact female values whereas replacement of both hormones together brought the GST activities to that of intact females. GRx ac tivities were brought to intact female values by replacement with estr ogen or progesterone, either singly or in combination. Neither ovariec tomy nor sex hormones replacement influenced the levels of WGSH, HGSH and GPx activities. Carcinogen administration to intact rats increased all the parameters measured. Ovariectomized rats treated with carcino gen showed lower GPx and GRx activities at 2 mths. However, replacemen t with either progesterone or combined estrogen and progesterone incre ased GPx and GRx activities to original values. On the other hand GST and GPx activities in ovariectomized rats which had carcinogen treatme nt were lower than intact rats after 5 mths. Replacement with hormones either singly or both brought GST and GPx activities up to intact rat levels receiving carcinogen. The levels of WGSH, HGSH and GRx activit ies (5 mths) in carcinogen treated rats were not influenced by ovariec tomy and/or hormone/s replacement. The results from this study suggest ed that ovariectomy reduced the severity of hepatocarcinogenesis which was restored by sex hormone/s replacement.