Bisphenol A interferes with thyroid specific gene expression

Bisphenol A (BPA) is an endocrine-disrupting chemical that leads to low-dose human exposure due to its ability to leach from chemically derived products, as polycarbonate plastics and epoxy resin. In addition to its known xeno-endocrine action, BPA exerts a wide range of metabolic effects. Despite the documented BPA exposure outcomes on synthesis of thyroid hormones, there are not any data available on its actions on the thyroid follicular cells, site of synthesis of the thyroid hormones. Recently, it has been shown that several environmental pollutants, as BPA, can exert a thyroid disrupting activity. In this study, we employed in vitro and in vivo (zebrafish) models to examine the effects of BPA in regulating the expression of genes involved in the thyroid hormone synthesis and of their transcriptional regulators at BPA doses as low as 10(-9)M, a dose that is environmentally pertinent and far below the one detected in infants plasma. In both systems we could detect an altered expression of the genes involved in thyroid hormones synthesis and of thyroid specific transcriptional factors in BPA dose and time dependent manner. Our results suggest that BPA exerts a direct effect on thyroid follicular cell. We show that these cells can "sense" very low amount of BPA. Thus they, potentially, represent an ideal in vitro system to develop assays to detect BPA and other pollutants with thyroid disrupting activity at level far below the ones considered to be environmental relevant. Moreover, this report may provide new insight into the mode of BPA-induced deregulation of physiological processes as well as on the extensively debated molecular pathways underlying its biological activities.