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

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 TR/β specific reporter gene assays. For this purpose, the effects of compounds on 3,3′,5-triiodothyronine (T₃)-induced TR- or TRβ-activation were tested in green monkey kidney fibroblast (CV-1) cells transiently transfected with Xenopus TRs and a luciferase reporter gene. The T₃-like BDE-OH and diiodobiphenyl (DIB) increased T₃-induced TR-activation, but not T₃-induced TRβ-activation. BDE28 (100 nM) did not act via TR, but almost tripled T₃-induced TRβ-activation relative to T₃ at its EC₅₀. BDE206 (100 nM) was antagonistic on both TRs with a maximum repression −54% relative to T₃ at its EC₅₀. 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 T₃-induced TRs.