Inhibition of rainbow trout (Oncorhynchus mykiss) estrogen receptor activity by cadmium
Inhibition of rainbow trout (Oncorhynchus mykiss) estrogen receptor activity by cadmium
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DOI：
10.1095/biolreprod63.1.259
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发表时间：
2000-07-01
影响因子：
3.6
通讯作者：
Pakdel, F
中科院分区：
文献类型：
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作者：
Le Guével, R;Petit, FG;Pakdel, F
本研究的目的是确定是否镉介导的抑制卵黄发生的鱼从污染地区或实验暴露于镉相关的雌激素受体的转录活性的修改。利用表达虹鳟（Oncorhynchos mykiss）雌二醇受体或人雌二醇受体的重组酵母系统，研究镉暴露对虹鳟雌二醇受体转录活性的直接影响。在重组酵母中，镉减少雌二醇刺激的雌激素反应报告基因的转录。在体外结合试验表明，镉不影响配体结合的受体。酵母单杂交和双杂交试验表明，雌二醇诱导的构象变化和受体二聚化不受镉的影响，相反，DNA结合的雌二醇受体，其同源元素显着减少凝胶阻滞试验。这项研究提供了支持镉是一种重要的内分泌干扰物，通过对雌二醇受体转录活性的直接影响，并可能会影响一些雌激素信号通路的观点的机制数据。
This study was conducted to determine if the cadmium-mediated inhibition of vitellogenesis observed in fish collected from contaminated areas or undergoing experimental exposure to cadmium correlated with modification in the transcriptional activity of the estrogen receptor. A recombinant yeast system expressing rainbow trout (Oncorhynchos mykiss) estradiol receptor or human estradiol receptor was used to evaluate the direct effect of cadmium exposure on estradiol receptor transcriptional activity. In recombinant yeast, cadmium reduced the estradiol-stimulated transcription of an estrogen-responsive reporter gene. In vitro-binding assays indicated that cadmium did not affect ligand binding to the receptor. Yeast one- and two-hybrid assays showed that estradiol-induced conformational changes and receptor dimerization were not affected by cadmium; conversely, DNA binding of the estradiol receptor to its cognate element was dramatically reduced in gel retardation assay. This study provides mechanistic data supporting the idea that cadmium is an important endocrine disrupter through a direct effect on estradiol receptor transcriptional activity and may affect a number of estrogen signaling pathways.