• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >4-HYDROXYLATION OF ESTRADIOL BY HUMAN UTERINE MYOMETRIUM AND MYOMA MICROSOMES - IMPLICATIONS FOR THE MECHANISM OF UTERINE TUMORIGENESIS
【24h】

4-HYDROXYLATION OF ESTRADIOL BY HUMAN UTERINE MYOMETRIUM AND MYOMA MICROSOMES - IMPLICATIONS FOR THE MECHANISM OF UTERINE TUMORIGENESIS

机译：子宫子宫肌层和子宫肌瘤微粒体对雌二醇的4-羟基氧化作用-对子宫蠕虫发生机理的意义

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Estradiol is converted to catechol estrogens via 2- and 4-hydroxylation by cytochrome P450 enzymes, 4-Hydroxyestradiol elicits biological activities distinct from estradiol, most notably an oxidant stress response induced by free radicals generated by metabolic redox cycling reactions. In this study, we have examined 2- and 4-hydroxylation of estradiol by microsomes of human uterine myometrium and of associated myomata. In all eight cases studied, estradiol 4-hydroxylation by myoma has been substantially elevated relative to surrounding myometrial tissue (minimum, 2-fold; mean, 5-fold), Estradiol 2-hydroxylation in myomata occurs at much lower rates than 4-hydroxylation (ratio of 4-hydroxyestradiol/2-hydroxyestradiol, 7.9 +/- 1.4) and does not significantly differ from rates in surrounding myometrial tissue. Rates of myometrial 2-hydroxylation of estradiol were also not significantly different from values in patients without myomata, We have used various inhibitors to establish that 4-hydroxylation is catalyzed by a completely different cytochrome P450 than 2-hydroxylation. In myoma, alpha-naphthoflavone and a set of ethynyl polycyclic hydrocarbon inhibitors (5 mu M) each inhibited 4-hydroxylation more efficiently (up to 90%) than 2-hydroxylation (up to 40%), indicating > 10-fold differences in K-i (< 0,5 mu M vs, > 5 mu M). These activities were clearly distinguished from the selective 2-hydroxylation of estradiol in placenta by aromatase reported previously (low K-m, inhibition by Fadrozole hydrochloride or ICI D1033). 4-Hydroxylation was also selectively inhibited relative to 2-hydroxylation by antibodies raised against cytochrome P450 IB1 (rat) (53 vs. 17%), These data indicate that specific 4-hydroxylation of estradiol in human uterine tissues is catalyzed by a form(s) of cytochrome P450 related to P450 IB1, which contribute(s) little to 2-hydroxylation, This enzyme(s) is therefore a marker for uterine myomata and may play a role in the etiology of the tumor. [References: 35]
机译：雌二醇通过细胞色素P450酶经2-和4-羟基化反应转化为邻苯二酚雌激素，4-羟基雌二醇引发不同于雌二醇的生物学活性，最显着的是由氧化还原循环反应产生的自由基诱导的氧化应激反应。在这项研究中，我们检查了人子宫肌层和相关肌瘤微粒体的雌二醇的2-羟基和4-羟基化。在所研究的全部八种情况下，相对于周围的子宫肌层组织，肌瘤引起的雌二醇4-羟基化程度显着提高（最低2倍；平均5倍），肌瘤中雌二醇2-羟基化的发生率远低于4-羟基化（4-羟基雌二醇/ 2-羟基雌二醇的比率，7.9 +/- 1.4），与周围子宫肌层组织的比率没有显着差异。雌二醇的子宫肌层2-羟基化率与没有肌瘤的患者的值也无显着差异。我们使用了多种抑制剂来确定4-羟基化是由与2-羟基化完全不同的细胞色素P450催化的。在肌瘤中，α-萘黄酮和一组乙炔基多环烃抑制剂（5μM）分别比2-羟基化（最高40％）更有效地抑制4-羟基化（最高90％），表明两者之间的差异> 10倍Ki（<0.5μMvs，> 5μM）。这些活性与先前报道的芳香化酶（低K-m，受Fadrozole盐酸盐或ICI D1033的抑制）与胎盘中雌二醇的选择性2-羟基化有明显区别。相对于2-羟基化作用，针对细胞色素P450 IB1（大鼠）产生的抗体也选择性抑制4-羟基化作用（53％vs.17％）。这些数据表明，人子宫组织中雌二醇的特异性4-羟基化作用是通过一种形式（一个或多个与P450 IB1有关的细胞色素P450，它们对2-羟基化的贡献很小。因此，该酶是子宫肌瘤的标志物，并可能在肿瘤的病因中起作用。 [参考：35]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号