Binding Affinity of PRTR Chemicals to Various Human Nuclear Receptors

Since the 1990s, population decreases, reproductive anomalies and malformations of highly aquatic animals have been increasingly reported. One possible cause is considered to be endocrine disruptive effects induced by environmental contaminants through a direct interaction with nuclear receptors, not only with steroid hormone receptors but also with other ones. In this study, we examined the binding affinities of 20 chemicals, which are registered in the Japanese Pollutant Release and Transfer Register (PRTR) and have been abundantly discharged into aquatic environments to eight human nuclear receptors and assessed their potential endocrine disruptive effects. Of the 20 PRTR chemicals tested, nonylphenol diethoxylate, telephthalic acid (TPA), and linear dodecyl-benzensulfonate (DBS) bound to at least two receptors at high concentrations. TPA and DBS enhanced the activities of both retinoic acid receptor (RAR) γ and vitamin D receptor (VDR) in a dose-dependent manner. This suggests that TPA and DBS may disturb the vitamin D endocrine functions mediated by a VDR-VDR homodimer or a VDR-RAR heterodimer. Also, our results indicate that endocrine disruptors unsuspected under the current assessment criteria could potentially bind to various nuclear receptors and disrupt endocrine systems mediated by such receptors.