Katsu Yoshinao, Lange Anke, Urushitani Hiroshi, Ichikawa Rie, Paull Gregory C, Cahill Laura L, Jobling Susan, Tyler Charles R, Iguchi Taisen
Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, 444-8787, Japan.
Environ Sci Technol. 2007 May 1;41(9):3368-74. doi: 10.1021/es062797l.
Wild male roach (Rutilus rutilus) living in U.K. rivers contaminated with estrogenic effluents from wastewater treatment works show feminized responses and have a reduced reproductive capability, but the chemical causation of sexual disruption in the roach has not been established. Feminized responses were induced in male roach exposed to environmentally relevant concentrations of the pharmaceutical estrogen 17alpha-ethinylestradiol, EE2 (up to 4 ng/ L), during early life (from fertilization to 84 days posthatch, dph), and these effects were signaled by altered patterns of expression of two cloned roach estrogen receptor (ER) subtypes, ERalpha. and ERbeta, in the brain and gonad/ liver. Transactivation assays were developed for both roach ER subtypes and the estrogenic potencies of steroidal estrogens differed markedly at the different ER subtypes. EE2 was by far the most potent chemical, and estrone (E1, the most prevalent environmental steroid in wastewater discharges) was equipotent with estradiol (E2) in activating the ERs. Comparison of the EC50 values for the compounds tested showed that ERbeta was 3-21-fold more sensitive to natural steroidal estrogens and 54-fold more sensitive to EE2 as compared to ERalpha. These findings add substantial support to the hypothesis that steroidal estrogens play a significant role in the induction of intersex in roach populations in U.K. rivers and that the molecular approach described could be usefully applied to understand interspecies sensitivity to xenoestrogens.
生活在英国河流中的野生雄性拟鲤（Rutilus rutilus），这些河流受到来自污水处理厂含雌激素废水的污染，它们表现出雌性化反应且繁殖能力下降，但拟鲤性发育异常的化学成因尚未明确。在幼鱼期（从受精到孵化后84天，dph），将雄性拟鲤暴露于环境相关浓度的药物雌激素17α-乙炔雌二醇（EE2，高达4 ng/L）中，可诱导其出现雌性化反应，并且这些影响通过大脑、性腺/肝脏中两种克隆的拟鲤雌激素受体（ER）亚型ERα和ERβ表达模式的改变得以体现。针对两种拟鲤ER亚型开发了反式激活分析方法，甾体雌激素在不同ER亚型上的雌激素活性差异显著。EE2是迄今为止活性最强的化学物质，雌酮（E1，污水排放中最普遍的环境甾体）在激活ER方面与雌二醇（E2）效力相当。对所测试化合物的EC50值进行比较表明，与ERα相比，ERβ对天然甾体雌激素的敏感性高3至21倍，对EE2的敏感性高54倍。这些发现为甾体雌激素在英国河流拟鲤种群雌雄同体诱导中起重要作用这一假说提供了有力支持，并且所描述的分子方法可有效用于理解物种间对异种雌激素的敏感性。
