Estrogen receptor (ER)-mediated activation by endocrine disrupting chemicals (EDCs)

Abstract

Studies have shown that many synthetic and natural chemicals, classified as endocrine-disrupting chemicals (EDCs), disrupt the normal endocrine system function in both humans and animal species. In our recent study, we used human HepG2 (hepatocellular cancer), HeLa (cervical cancer), and Ishikawa (endometrial cancer) cell lines to analyze the estrogenic effects of a set of known EDCs on the ERs. Our studies demonstrate the mechanistic importance of chemical structure similarities and cell type/promoter specificity when evaluating the potential activities of EDCs. The synthetic EDCs, such as BPA and its analogs, mainly affect ERα and can act as both agonists and antagonists in a dose-dependent manner. The natural EDCs (daidzein and genistein) are stronger estrogens due to their estrogenic activations for both ERα and ERβ. Most importantly, the dosage determines whether a specific endocrine disrupting compound is beneficial or toxic to the human population and one mechanism cannot explain the complexity of these compounds actions.