There is growing concern about the environmentally relevant concentrations of new emerging persistent organic pollutants, such as perfluorinated compounds and pharmaceuticals, which are found to bioaccumulate in aquatic organisms at concentrations suspected to cause reproductive toxicity due to the activation of estrogen receptor (ER) α and β subtypes. Here, we use a combined in silico and in vitro approach to evaluate the impact of perfluorononanoic acid (PFNA) and Enalapril (ENA) on grey mullet (Mugil cephalus) hepatic estrogen signaling pathway. ENA had weak agonist activity on ERα while PFNA showed moderate to high agonist binding to both ERs. According to these effects, hepatocytes incubation for 48 h to PFNA resulted in a concentration-dependent upregulation of ER and vitellogenin gene expression profiles, whereas only a small increase was observed in ERα mRNA levels for the highest ENA concentration. These data suggest a structure–activity relationship between hepatic ERs and these emerging pollutants.

中文翻译：

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使用来自灰鲻鱼 (Mugil Cephalus) 的原代肝细胞研究新出现的持久性污染物的雌激素内分泌影响的计算机模拟和体外研究

人们越来越关注新出现的持久性有机污染物的环境相关浓度，例如全氟化合物和药物，发现这些物质在水生生物中生物积累，浓度怀疑由于雌激素受体 (ER) α 和β 亚型。在这里，我们使用计算机模拟和体外相结合的方法来评估全氟壬酸 (PFNA) 和依那普利 (ENA) 对鲻鱼 ( Mugil cephalus) 的影响) 肝脏雌激素信号通路。ENA 对 ERα 的激动剂活性较弱，而 PFNA 对两种 ER 均表现出中度至高度的激动剂结合。根据这些效应，肝细胞与 PFNA 孵育 48 小时导致 ER 和卵黄蛋白原基因表达谱的浓度依赖性上调，而在最高 ENA 浓度下仅观察到 ERα mRNA 水平的小幅增加。这些数据表明肝内质网与这些新出现的污染物之间存在构效关系。