Inazu N, Inaba N, Satoh T
Department of Pharmacology and Toxicology, Tokyo College of Pharmacy, Japan.
Biochem Pharmacol. 1990 Dec 1;40(11):2495-502. doi: 10.1016/0006-2952(90)90091-x.
In the present study, the enhancing effect of synthetic estrogen on ovarian carbonyl reductase, a new prostaglandin (PG)-metabolizing enzyme, was investigated, and the antagonistic effect of antiestrogen on this enhancement was examined in immature rats. Ovarian carbonyl reductase activity towards 13,14-dihydro-15-keto-PGF2 alpha (15KD-PGF2 alpha), 4-benzoylpyridine (4BP) and menadione was determined photometrically and radiochemically, and quantitation of ovarian carbonyl reductase content was performed by Western blot analysis. Diethylstilbestrol (DES) and hexestrol (HX) enhanced the increasing effect of human chorionic gonadotropin (hCG) on ovarian carbonyl reductase activity and content when these synthetic estrogens (0.2 mg/kg) were administered for 3 days from 26 days of age, before hCG treatment. On the other hand, tamoxifen, which inhibits the binding of estradiol to the estrogen receptor, significantly prevented estradiol (E2) from enhancing the effect of hCG on ovarian carbonyl reductase. Furthermore, the ovarian carbonyl reductase activities towards the three substrates correlated well with the ovarian carbonyl reductase content. These results indicate that ovarian carbonyl reductase in immature rats may be regulated by a specific increase in the ovarian response to luteinizing hormone mediated by estrogen receptor.
在本研究中，研究了合成雌激素对一种新的前列腺素（PG）代谢酶——卵巢羰基还原酶的增强作用，并在未成熟大鼠中检测了抗雌激素对这种增强作用的拮抗作用。通过光度法和放射化学法测定了卵巢羰基还原酶对13,14-二氢-15-酮-PGF2α（15KD-PGF2α）、4-苯甲酰吡啶（4BP）和甲萘醌的活性，并通过蛋白质免疫印迹分析对卵巢羰基还原酶含量进行了定量。当从26日龄开始连续3天给予这些合成雌激素（0.2mg/kg），在人绒毛膜促性腺激素（hCG）处理之前，己烯雌酚（DES）和己烷雌酚（HX）增强了hCG对卵巢羰基还原酶活性和含量的增加作用。另一方面，抑制雌二醇与雌激素受体结合的他莫昔芬显著阻止了雌二醇（E2）增强hCG对卵巢羰基还原酶的作用。此外，卵巢羰基还原酶对三种底物的活性与卵巢羰基还原酶含量密切相关。这些结果表明，未成熟大鼠的卵巢羰基还原酶可能受雌激素受体介导的卵巢对促黄体生成素反应的特异性增加调节。
