Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: A novel pathway explaining the estrogenic activity of PCBs
Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: A novel pathway explaining the estrogenic activity of PCBs
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DOI：
10.1210/en.141.5.1897
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发表时间：
2000-05-01
期刊：
影响因子：
4.8
通讯作者：
Visser, TJ
中科院分区：
文献类型：
--
作者：
Kester, MHA;Bulduk, S;Visser, TJ
多氯联苯（PCBs）是一种持久性环境污染物，对动物的性发育和生殖功能具有多种毒性作用。多氯联苯的雌激素效应可能部分由羟基化的多氯联苯代谢物（PCB-OH）介导，但它们产生的机制尚不清楚。多氯联苯和多氯联苯羟基化合物对α和β雌激素受体亚型的亲和力都很低。在本研究中，我们证明，各种环境相关的PCB-OH是人类雌激素磺基转移酶的非常有效的抑制剂，强烈表明，他们间接诱导雌激素活性增加雌二醇在靶组织中的生物利用度。
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants which exert a variety of toxic effects in animals, including disturbances of sexual development and reproductive function. The estrogenic effects of PCBs may be mediated in part by hydroxylated PCB metabolites (PCB-OHs), but the mechanisms by which they are brought about are not understood. PCBs as well as PCB-OHs show low affinities for both alpha and beta estrogen receptor isoforms. In the present study we demonstrate that various environmentally relevant PCB-OHs are extremely potent inhibitors of human estrogen sulfotransferase, strongly suggesting that they indirectly induce estrogenic activity by increasing estradiol bioavailability in target tissues.