Thyroid hormone receptor isoform selectivity of thyroid hormone disrupting compounds quantified with an in vitro reporter gene assay

Abstract

Some compounds, including brominated diphenyl ethers (BDEs), can interfere with thyroid hormone (TH) receptor (TR)-mediated TH-signalling. In this study, the TR isoform selectivity of some TH disrupting compounds was investigated with TRα/β specific reporter gene assays. For this purpose, the effects of compounds on 3,3′,5-triiodothyronine (T 3)-induced TRα- or TRβ-activation were tested in green monkey kidney fibroblast (CV-1) cells transiently transfected with Xenopus TRs and a luciferase reporter gene. The T 3-like BDE-OH and diiodobiphenyl (DIB) increased T 3-induced TRα-activation, but not T 3-induced TRβ-activation. BDE28 (100 nM) did not act via TRα, but almost tripled T 3-induced TRβ-activation relative to T 3 at its EC 50. BDE206 (100 nM) was antagonistic on both TRs with a maximum repression −54% relative to T 3 at its EC 50. Contrary to previous results obtained with the T-screen, HBCD was inactive. The present study illustrates the importance of testing potential TH disrupting compounds in model systems that enable independent characterization of effects on both T 3-induced TRs.