Inhibition of Thyroid HormoneSulfotransferase Activityby Brominated Flame Retardants and Halogenated Phenolics.

Many halogenated organic contaminants(HOCs) are considered endocrinedisruptors and affect the hypothalamic–pituitary–thyroidaxis, often by interfering with circulating levels of thyroid hormones(THs). We investigated one potential mechanism for TH disruption,inhibition of sulfotransferase activity. One of the primary rolesof TH sulfation is to support the regulation of biologically activeT3 through the formation of inactive THs. We investigated TH sulfotransferaseinhibition by 14 hydroxylated polybrominated diphenyl ethers (OH BDEs),BDE 47, triclosan, and fluorinated, chlorinated, brominated, and iodinatedanalogues of 2,4,6-trihalogenated phenol and bisphenol A (BPA). Anew mass spectrometry-based method was also developed to measure theformation rates of 3,3′-T2 sulfate (3,3′-T2S). Usingpooled human liver cytosol, we investigated the influence of theseHOCs on the sulfation of 3,3′-T2, a major substrate for THsulfation. For the formation of 3,3′-T2S, the Michaelis constant(Km) was 1070 ± 120 nM and the Vmaxwas 153 ± 6.6 pmol min–1(mg of protein)−1. All chemicals investigatedinhibited sulfotransferase activity with the exception of BDE 47.The 2,4,6-trihalogenated phenols were the most potent inhibitors followedby the OH BDEs and then halogenated BPAs. The IC50valuesfor the OH BDEs were primarily in the low nanomolar range, which maybe environmentally relevant. In silicomolecularmodeling techniques were also used to simulate the binding of OH BDEto SULT1A1. This study suggests that some HOCs, including antimicrobialchemicals and metabolites of flame retardants, may interfere withTH regulation through inhibition of sulfotransferase activity. [ABSTRACT FROM AUTHOR]