title: 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 (100nM) did not act via TRα, but almost tripled T(3)-induced TRβ-activation relative to T(3) at its EC(50). BDE206 (100nM) 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.
authors.affiliation: Toxicology Section, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
authors.forename: Merijn
authors.initials: M
authors.lastname: Schriks
authors.forename: Julie M
authors.initials: JM
authors.lastname: Roessig
authors.forename: Albertinka J
authors.initials: AJ
authors.lastname: Murk
authors.forename: J David
authors.initials: JD
authors.lastname: Furlow