Department of Biology, Centre for Advanced Research in Environmental Genomics, University of Ottawa Ottawa, ON, Canada.
Front Endocrinol (Lausanne). 2011 Dec 2;2:83. doi: 10.3389/fendo.2011.00083. eCollection 2011.
Endocrine disrupting chemicals are adversely affecting the reproductive health and metabolic status of aquatic vertebrates. Estrone is often the dominant natural estrogen in urban sewage, yet little is known about its environmental fate and biological effects. Increased use of UV-B radiation for effluent treatments, and exposure of effluents to sunlight in holding ponds led us to examine the effects of environmentally relevant levels of UV-B radiation on the photodegradation potential of estrone. Surprisingly, UV-B-mediated degradation leads to the photoproduction of lumiestrone, a little known 13α-epimer form of estrone. We show for the first time that lumiestrone possesses novel biological activity. In vivo treatment with estrone stimulated estrogen receptor (ER) α mRNA production in the male goldfish liver, whereas lumiestrone was without effect, suggesting a total loss of estrogenicity. In contrast, results from in vitro ER-dependent reporter gene assays indicate that lumiestrone showed relatively higher estrogenic potency with the zebrafish ERβ2 than zfERα, suggesting that it may act through an ERβ-selectivity. Lumiestrone also activated human ERs. Microarray analysis of male goldfish liver following in vivo treatments showed that lumiestrone respectively up- and down-regulated 20 and 69 mRNAs, which was indicative of metabolic upsets and endocrine activities. As a photodegradation product from a common estrogen of both human and farm animal origin, lumiestrone is present in sewage effluent, is produced from estrone upon exposure to natural sunlight and should be considered as a new environmental contaminant.
内分泌干扰化学物质正在对水生脊椎动物的生殖健康和代谢状况产生不利影响。雌酮通常是城市污水中主要的天然雌激素,但对其环境归宿和生物效应知之甚少。紫外线-B 辐射在废水处理中的应用增加,以及废水在储水池中暴露在阳光下,促使我们研究环境相关水平的紫外线-B 辐射对雌酮光降解潜力的影响。令人惊讶的是,紫外线-B 介导的降解导致了 lumie 雌酮的光生产,这是一种鲜为人知的雌酮 13α-差向异构体形式。我们首次表明,lumie 雌酮具有新的生物学活性。体内用雌酮处理刺激雄性金鱼肝脏中的雌激素受体 (ER)α mRNA 产生,而 lumie 雌酮没有作用,表明完全丧失了雌激素性。相比之下,来自体外 ER 依赖性报告基因测定的结果表明,lumie 雌酮对斑马鱼 ERβ2 的雌激素活性相对高于 zfERα,表明它可能通过 ERβ 选择性起作用。Lumie 雌酮还激活了人类 ER。体内处理后雄性金鱼肝脏的微阵列分析表明,lumie 雌酮分别上调和下调了 20 和 69 个 mRNA,这表明存在代谢紊乱和内分泌活动。作为一种来自人类和农场动物来源的常见雌激素的光降解产物,lumie 雌酮存在于污水废水中,在暴露于自然阳光时会从雌酮产生,应被视为一种新的环境污染物。