Becedas L, Bengtson Ahlberg M
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Biochem Pharmacol. 1995 Feb 14;49(4):503-9. doi: 10.1016/0006-2952(94)00434-n.
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.(ABSTRACT TRUNCATED AT 400 WORDS)
研究了大鼠卵巢在发情周期不同阶段代谢外源性物质的总能力的变化。测定了卵巢中结合酶、酚UDP-葡萄糖醛酸基转移酶(pUDPGT;EC 2.4.1.17)、酚磺基转移酶(pST;EC 2.8.2.1)和谷胱甘肽转移酶(EC 2.5.1.18)的水平,并与相应的肝脏活性进行比较。此外,还测定了另外两种解毒酶过氧化氢酶(EC 1.11.1.6)和NAD(P)H:醌氧化还原酶(EC 1.6.99.2)。为了研究激素对解毒酶的影响,根据发情周期阶段对成熟大鼠进行了特征描述。未成熟大鼠分别用孕马血清促性腺激素(PMSG)处理2或3天,以使卵巢中分别富含排卵前卵泡或黄体。本研究表明,与未处理的未成熟大鼠的卵巢相比,富含黄体的卵巢中卵巢pUDPGT和pST活性分别增加了936%和175%。还注意到,与发情前期相比,发情周期间情期阶段成熟大鼠的这些活性增加。与未处理的大鼠相比,卵巢富含排卵前卵泡的未成熟大鼠肝脏中的pUDPGT活性显著增加(1.6倍)。用PMSG处理(“超刺激”)的成熟大鼠卵巢中pST和pUDPGT活性均增加,而肝脏中只有pST活性因这种处理而增加。卵巢谷胱甘肽转移酶活性被证明不依赖于与发情周期相关的激素波动。然而,与未处理的未成熟大鼠相比,用PMSG处理的成熟大鼠肝脏中该活性增加了2倍。在卵巢线粒体部分中发现的过氧化氢酶活性比胞质部分高约10倍,与激素状态无关。此外,我们发现,在用PMSG处理的未成熟大鼠的线粒体部分中,无论富含排卵前卵泡还是黄体,过氧化物酶体过氧化氢酶活性均显著增加1.4倍。PMSG处理后,未成熟大鼠肝脏胞质中的过氧化氢酶活性降低了几倍。我们未发现发情周期期间卵巢NAD(P)H:醌氧化还原酶活性有任何变化,而在肝脏中,该活性在黄体期降低,在用PMSG处理的成熟大鼠中也是如此。从本研究以及我们实验室早期的研究中,我们得出结论,发情周期激素引起的卵巢中主要的7,12-二甲基苯并(a)蒽(DMBA)代谢I相酶的周期性变化并未伴随相应II相酶活性的增加。(摘要截短为400字)