Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, and Department of Basic Biology, The Graduate School for Advanced Studies (SOKENDAI) , Okazaki, Aichi 444-8787, Japan.
Environ Sci Technol. 2014 May 6;48(9):5254-63. doi: 10.1021/es5002659. Epub 2014 Apr 14.
Exposure to estrogenic endocrine disrupting chemicals (EDCs) induces a range of adverse effects, notably on reproduction and reproductive development. These responses are mediated via estrogen receptors (ERs). Different species of fish may show differences in their responsiveness to environmental estrogens but there is very limited understanding on the underlying mechanisms accounting for these differences. We used custom developed in vitro ERα reporter gene assays for nine fish species to analyze the ligand- and species-specificity for 12 environmental estrogens. Transcriptonal activities mediated by estradiol-17β (E2) were similar to only a 3-fold difference in ERα sensitivity between species. Diethylstilbestrol was the most potent estrogen (∼ 10-fold that of E2) in transactivating the fish ERαs, whereas equilin was about 1 order of magnitude less potent in all species compared to E2. Responses of the different fish ERαs to weaker environmental estrogens varied, and for some considerably. Medaka, stickleback, bluegill and guppy showed higher sensitivities to nonylphenol, octylphenol, bisphenol A and the DDT-metabolites compared with cyprinid ERαs. Triclosan had little or no transactivation of the fish ERαs. By constructing ERα chimeras in which the AF-containing domains were swapped between various fish species with contrasting responsiveness and subsequent exposure to different environmental estrogens. Our in vitro data indicate that the LBD plays a significant role in accounting for ligand sensitivity of ERα in different species. The differences seen in responsiveness to different estrogenic chemicals between species indicate environmental risk assessment for estrogens cannot necessarily be predicted for all fish by simply examining receptor activation for a few model fish species.
暴露于雌激素内分泌干扰化学物质（EDCs）会引起一系列不良反应，特别是对生殖和生殖发育。这些反应是通过雌激素受体（ERs）介导的。不同种类的鱼类可能对环境雌激素的反应不同，但对于导致这些差异的潜在机制知之甚少。我们使用为 9 种鱼类开发的定制体外 ERα报告基因测定法来分析 12 种环境雌激素的配体和物种特异性。雌二醇-17β（E2）介导的转录活性与物种间 ERα 敏感性的差异仅为 3 倍。己烯雌酚是最强的雌激素（比 E2 强约 10 倍），可激活鱼类 ERα，而 equilin 在所有物种中的活性比 E2 低 1 个数量级。不同鱼类 ERα 对较弱环境雌激素的反应不同，有些则相差很大。与鲤鱼 ERα相比，青鳉、棘鱼、蓝鳃太阳鱼和孔雀鱼对壬基酚、辛基酚、双酚 A 和 DDT 代谢物表现出更高的敏感性。三氯生对鱼类 ERα的激活作用很小或没有。通过构建 ERα嵌合体，将含有 AF 的结构域在具有不同反应性的不同鱼类之间交换，然后用不同的环境雌激素进行暴露。我们的体外数据表明，LBD 在不同物种中 ERα 配体敏感性的差异中起着重要作用。不同物种对不同雌激素化学物质的反应性差异表明，对于雌激素的环境风险评估，不能仅仅通过检查少数模式鱼类的受体激活来预测所有鱼类。
