Endocrine-Disrupting Chemicals (EDCs): In Vitro Mechanism of Estrogenic Activation and Differential Effects on ER Target Genes

• DOI: 10.1289/ehp.1205951
• Publication Date: 2013-02-05T20:07:42Z
• Authors: Yin Li; Colin J. Luh; Katherine A. Burns; Yukitomo Arao; Zhongliang Jiang; Christina T. Teng; Raymond R. Tice; Kenneth S. Korach
• Keywords: Estrogen receptor alpha

Endocrine-disrupting chemicals (EDCs) influence the activity of estrogen receptors (ERs) and alter function endocrine system. However, diversity EDC effects mechanisms action are poorly understood.We examined agonistic EDCs through ERα ERβ. We also investigated on ER-mediated target genes.HepG2 HeLa cells were used to determine ERβ via luciferase reporter assay. Ishikawa stably expressing changes in endogenous ER gene expression by EDCs.Twelve categorized into three groups basis product class similarity chemical structure. As shown analysis, act as agonists a cell type- promoter-specific manner. Bisphenol A, bisphenol AF, 2-2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (group 1) strongly activated responsive element (ERE)-mediated responses. Daidzein, genistein, kaempferol, coumestrol 2) both ERE-mediated activities. Endosulfan kepone 3) weakly ERα. Only few significantly "tethered" mechanism or Results real-time polymerase chain reaction indicated that A AF consistently genes, but activities other compound specific.Although with similar structures (in same group) tended have comparable activities, structure did not correlate previously reported ligand binding affinities EDCs. Using ERα-stable cells, we observed differentially induced genes.