Jellinck P H, Newcombe A M
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
J Steroid Biochem. 1988 Dec;31(6):887-90. doi: 10.1016/0022-4731(88)90329-9.
The action of a number of different divalent metal ions on the rat liver microsomal release of 3H2O from estradiol and 2-hydroxyestradiol labeled with 3H at C-2 or C-4 was investigated. Cu2+ at low concentration (10 microM) produced a marked and specific inhibition of the 2-hydroxylation of estradiol with virtually no effect on the further oxidative activation of catechol estrogen. In contrast, Zn2+ inhibited the interaction of 2-hydroxyestradiol with microsomal protein as measured by the release of 3H from C-4 of the labeled steroids but did not influence 2-hydroxylation, except at high concentration. Other metal ions tested produced little or no change. Cu2+ inhibited the irreversible binding of estradiol to protein but activated this reaction with the catechol estrogen as substrate. The action of both Cu2+ and Zn2+ was reversed by glutathione. The differential effect of these metal ions on estrogen metabolism gives additional support for two different mechanisms in the cytochrome P-450-catalyzed formation of catechol estrogens and their further activation to form protein conjugates.
研究了多种不同二价金属离子对大鼠肝脏微粒体从 C-2 或 C-4 位标记有 3H 的雌二醇和 2-羟基雌二醇释放 3H2O 的作用。低浓度（10 microM）的 Cu2+对雌二醇的 2-羟化产生显著且特异性的抑制，而对儿茶酚雌激素的进一步氧化活化几乎没有影响。相比之下，Zn2+抑制了标记类固醇 C-4 位 3H 的释放所测定的 2-羟基雌二醇与微粒体蛋白的相互作用，但除高浓度外不影响 2-羟化。测试的其他金属离子几乎没有产生变化或没有变化。Cu2+抑制雌二醇与蛋白的不可逆结合，但以儿茶酚雌激素为底物时激活该反应。Cu2+和 Zn2+的作用都被谷胱甘肽逆转。这些金属离子对雌激素代谢的差异作用为细胞色素 P-450 催化儿茶酚雌激素的形成及其进一步活化为蛋白结合物的两种不同机制提供了额外支持。
