Differential effects of phthalate esters on transcriptional activities via human estrogen receptors α and β, and androgen receptor

Some phthalates are suspected to disrupt the endocrine system, especially by mimicking estrogens. In this study, we characterized the activities of human estrogen receptor α (hERα), human estrogen receptor β (hERβ), and human androgen receptor (hAR) in the presence of 22 phthalates including 3 of their metabolites using highly sensitive reporter gene assays. Of the 22 compounds tested, several phthalate diesters with alkyl chains ranging in length from C3 to C6 exhibited not only hERα-mediated estrogenic activity, but also hERβ-mediated antiestrogenic activity in a dose-dependent manner. In addition, we found that some phthalate diesters possess hAR-mediated antiandrogenic activity. However, the phthalates having side chains with very short length (diethyl) or very long length (diheptyl), and three metabolites (monoesters) were found to have no effect on the activities of the three receptors. These results indicate that several phthalate esters simultaneously act as agonists and/or antagonists via one or more hormonal receptors, and interaction of phthalate esters with the estrogen and androgen receptors requires certain size and bulkiness with alkyl groups.