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

  • Schriks M
  • Roessig J
  • Murk A
 et al. 
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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 TR??/?? specific reporter gene assays. For this purpose, the effects of compounds on 3,3???,5-triiodothyronine (T3)-induced TR??- or TR??-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 TR??-activation. BDE28 (100 nM) did not act via TR??, but almost tripled T3-induced TR??-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. ?? 2006 Elsevier B.V. All rights reserved.

Author-supplied keywords

  • BDE206
  • Brominated flame retardants
  • Differential expression
  • HBCD
  • PHAHs
  • Transient transfections

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Authors

  • Merijn Schriks

  • Julie M. Roessig

  • Albertinka J. Murk

  • J. David Furlow

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