Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Seoul, 05006, Republic of Korea.
Department of Integrative Bioscience and Biotechnology, College of Life Science, Sejong University, Seoul, 05006, Republic of Korea.
Environ Pollut. 2019 May;248:774-781. doi: 10.1016/j.envpol.2019.02.069. Epub 2019 Feb 21.
Endocrine-disrupting chemicals (EDCs) are widely used in various consumer goods. Consequently, humans are constantly exposed to EDCs, which is associated with a variety of endocrine-related diseases. In this study, we demonstrated the effects of bisphenol A (BPA), benzyl butyl phthalate (BBP), and di(2-ethylhexyl) phthalate (DEHP) on estrogen receptor alpha (ERα) expression under normoxia and hypoxia. First, we confirmed the effects of EDCs on ER activity using OECD Test Guideline 455. Compared to the 100% activity induced by 1 nM 17-β-estradiol (positive control), BPA and BBP exhibited 50% ERα activation at concentrations of 1.31 μM and 4.8 μM, respectively. In contrast, and consistent with previous reports, DEHP did not activate ERα. ERα is activated and degraded by hypoxia in breast cancer cells. BPA, BBP, and DEHP enhanced ERα-mediated transcriptional activity under hypoxia. All three EDCs decreased ERα protein levels under hypoxia in MCF-7 cells. The transcriptional activity of hypoxia-inducible factor-1 was decreased and secretion of vascular endothelial growth factor (VEGF) was increased by BPA and BBP under hypoxia in MCF-7 cells, but not by DEHP. All three EDCs decreased the ERα protein expression level in Ishikawa human endometrial adenocarcinoma cells, and DEHP caused a weak decrease in VEGF secretion under hypoxia. These results demonstrate down-regulation of ERα by EDCs may influence the pathological state associated with hypoxia.
环境内分泌干扰物（EDCs）广泛应用于各种消费品中。因此，人类不断暴露于 EDCs 中，这与多种内分泌相关疾病有关。在本研究中，我们研究了双酚 A（BPA）、邻苯二甲酸丁基苄基酯（BBP）和邻苯二甲酸二（2-乙基己基）酯（DEHP）在常氧和低氧条件下对雌激素受体 alpha（ERα）表达的影响。首先，我们使用 OECD 测试指南 455 确认了 EDCs 对 ER 活性的影响。与 1nM 17-β-雌二醇（阳性对照）诱导的 100%活性相比，BPA 和 BBP 分别在 1.31μM 和 4.8μM 浓度下表现出 50%的 ERα 激活。相比之下，与先前的报道一致，DEHP 没有激活 ERα。在乳腺癌细胞中，缺氧会激活和降解 ERα。BPA、BBP 和 DEHP 在低氧条件下增强了 ERα 介导的转录活性。在 MCF-7 细胞中，三种 EDCs 均降低了 ERα 蛋白水平。在 MCF-7 细胞中，BPA 和 BBP 降低了低氧诱导因子-1 的转录活性，并增加了血管内皮生长因子（VEGF）的分泌，但 DEHP 没有。三种 EDCs 均降低了 Ishikawa 人子宫内膜腺癌细胞中的 ERα 蛋白表达水平，DEHP 在低氧下也导致 VEGF 分泌减弱。这些结果表明，EDCs 下调 ERα 可能会影响与缺氧相关的病理状态。
