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

Merijn Schriks; Julie M Roessig; Albertinka J Murk; J David Furlow

doi:10.1016/j.etap.2006.11.007

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

Environ Toxicol Pharmacol. 2007 May;23(3):302-7. doi: 10.1016/j.etap.2006.11.007. Epub 2006 Nov 18.

Authors

Merijn Schriks¹, Julie M Roessig, Albertinka J Murk, J David Furlow

Affiliation

¹ Toxicology Section, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.

PMID: 21783772
DOI: 10.1016/j.etap.2006.11.007

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.