Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences, Changchun, China.
College of Foreign Languages, Jilin Agricultural University, Changchun, China.
Toxicol Mech Methods. 2022 May;32(4):280-287. doi: 10.1080/15376516.2021.1998276. Epub 2021 Nov 14.
Phthalate esters (PAEs) are important pollutants in the environment, which can interfere with the endocrine system by mimicking estrogen. However, limited information is available on modulating the estrogen receptor (ER) of five PAEs including di (2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), benzyl butyl phthalate (BBP), diphenyl phthalate (DPhP) and dicyclohexyl phthalate (DCHP). This study evaluated the agonistic effects of PAEs on human ER. The cytotoxicity assay showed that there were a significant inhibition of the cell proliferation with treatment of five PAEs. Moreover, DPhP does-dependently enhanced ER-mediated transcriptional activity in the reporter gene assay. The increased expression of estrogen-responsive genes ( and ) was also observed in MCF-7 cells treated with DPhP. The result of molecular docking showed that DPhP tended to bind to the agonist conformation of ER compared with the antagonist conformation of ER, demonstrating its agonist characteristic that has been confirmed in the reporter gene assay. Thus, we found that DPhP may be evaluated as an ER agonist and it can interfere with the normal function of human ER.
邻苯二甲酸酯（PAEs）是环境中的重要污染物，它们可以通过模拟雌激素来干扰内分泌系统。然而，关于五种邻苯二甲酸酯（包括邻苯二甲酸二（2-乙基己基）酯（DEHP）、邻苯二甲酸二异壬酯（DINP）、邻苯二甲酸丁基苄基酯（BBP）、邻苯二甲酸二苯基酯（DPhP）和邻苯二甲酸二环己酯（DCHP））对雌激素受体（ER）的调节作用的信息有限。本研究评估了 PAEs 对人 ER 的激动作用。细胞毒性测定表明，五种 PAEs 的处理均显著抑制细胞增殖。此外，DPhP 在报告基因检测中依赖性地增强了 ER 介导的转录活性。在 DPhP 处理的 MCF-7 细胞中，还观察到雌激素反应基因（和）的表达增加。分子对接结果表明，与 ER 的拮抗剂构象相比，DPhP 倾向于与 ER 的激动剂构象结合，表明其在报告基因检测中已被证实的激动剂特征。因此，我们发现 DPhP 可能被评估为 ER 激动剂，并且它可以干扰人 ER 的正常功能。
