HORMONAL INFLUENCES OF DETOXICATION IN THE RAT OVARY ON ENZYMES IN COMPARISON WITH THE LIVER

Variations in the total capacity of the rat ovary to metabolize xenobi otics during different phases of the estrous cycle were studied. The l evel of the conjugating enzymes, phenol UDP-glucuronosyltransferase (p UDPGT; EC 2.4.1.17), phenol sulfotransferase (pST; EC 2.8.2.1) and glu tathione transferases (EC 2.5.1.18) was determined in the ovary and co mpared with the corresponding hepatic activities. In addition, catalas e (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 hormona l influences on detoxifying enzymes, mature rats were characterized wi th respect to their stage in the estrous cycle. Immature rats were tre ated with pregnant mare's serum gonadotropin (PMSG) for 2 or 3 days to enrich the ovaries in preovulatory follicles or corpora lutea, respec tively. The present study demonstrates that ovarian pUDPGT and pST act ivities are increased 936% and 175%, respectively, in ovaries enriched in corpora lutea compared to ovaries from untreated immature rats. In creases 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) i n immature rats with ovaries enriched in preovulatory follicles compar ed 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 tr ansferase activity proved not to be dependent on the hormonal fluctuat ions associated with the estrous cycle. However, in the liver of matur e rats treated with PMSG, this activity increased a-fold compared to t he untreated immature rats. The catalase activity found in the ovarian mitochondrial fraction was approx. 10-fold higher than in the cytosol ic 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 e nriched in preovulatory follicles and in corpora lutea. In the liver c ytosolic catalase activity decreased several-fold in immature rats fol lowing PMSG treatment. We did not find any variations in ovarian NAD(P )H:quinone oxidoreductase activity during the estrous cycle, whereas i n the liver this activity decreased in the luteal phase, as it did in mature rats treated with PMSG. From this study and earlier investigati ons in our laboratory, we conclude that cyclic variations due to hormo nes 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 tim e of ovulation may thus increase the risk of cellular damage, e.g. in the oocyte, during this period.