Hormonal influences of detoxication in the rat ovary on enzymes in comparison with the liver

Abstract

Variations in the total capacity of the rat ovary to metabolize xenobiotics during different phases of the estrous cycle were studied. The level of the conjugating enzymes, phenol UDP-glucuronosyltransferase (pUDPGT; EC 2.4.1.17), phenol sulfotransferase (pST; EC 2.8.2.1) and glutathione transferases (EC 2.5.1.18) was determined in the ovary and compared with the corresponding hepatic activities. In addition, catalase (EC 1.11.1.6) and NAD(P)H: quinone oxidoreductase (EC 1.6.99.2) two other detoxifying enzymes, were assayed. In order to study the hormonal influences on detoxifying enzymes, mature rats were characterized with respect to their stage in the estrous cycle. Immature rats were treated with pregnant mare's serum gonadotropin (PMSG) for 2 or 3 days to enrich the ovaries in preovulatory follicles or corpora lutea, respectively. The present study demonstrates that ovarian pUDPGT and pST activities are increased 936% and 175%, respectively, in ovaries enriched in corpora lutea compared to ovaries from untreated immature rats. Increases in these activities in mature rats during the metestrous stage of the estrous cycle compared to the proestrous stage were also noted. In the liver pUDPGT activity is increased significantly (1.6-fold) in immature rats with ovaries enriched in preovulatory follicles compared to untreated rats. Both ovarian pST and pUDPGT activities increased in mature rats treated with PMSG (“hyperstimulated”), while in the liver only pST was increased by such treatment. Ovarian glutathione transferase activity proved not to be dependent on the hormonal fluctuations associated with the estrous cycle. However, in the liver of mature rats treated with PMSG, this activity increased 2-fold compared to the untreated immature rats. The catalase activity found in the ovarian mitochondrial fraction was approx. 10-fold higher than in the cytosolic fraction, independent of the hormonal status. Moreover, we found a significant 1.4-fold increase in peroxisomal catalase activity in the mitochondrial fraction of immature rats treated with PMSG, both when enriched in preovulatory follicles and in corpora lutea. In the liver cytosolic catalase activity decreased several-fold in immature rats following PMSG treatment. We did not find any variations in ovarian NAD(P)H: quinone oxidoreductase activity during the estrous cycle, whereas in the liver this activity decreased in the luteal phase, as it did in mature rats treated with PMSG. From this study and earlier investigations in our laboratory, we conclude that cyclic variations due to hormones of the estrous cycle of the major 7,12-dimethylbenz(a)anthracene (DMBA)-metabolizing phase I enzymes in the ovary are not accompanied by increases in the activities of the corresponding phase II enzymes. An increased steady-state level of reactive intermediates around the time of ovulation may thus increase the risk of cellular damage, e.g. in the oocyte, during this period.