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

M. Schriks, J.M. Roessig, A.J. Murk, J.D. Furlow

Research output: Contribution to journalArticleAcademicpeer-review

44 Citations (Scopus)

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 alpha/beta specific reporter gene assays. For this purpose, the effects of compounds on 3,3',5-triiodothyronine (T-3)-induced TR alpha- or TR beta-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 TR alpha-activation, but not T-3-induced TRP-activation. BDE28 (100 nM) did not act via TR alpha, but almost tripled T-3-induced TRP-activation relative to T-3 at its EC50. BDE206 (100 nM) was antagonistic on both TRs with a maximum repression -54% relative to T-3 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. (c) 2006 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)302-307
JournalEnvironmental Toxicology and Pharmacology
Volume23
Issue number3
DOIs
Publication statusPublished - 2007

Keywords

  • halogenated aromatic-hydrocarbons
  • brominated flame retardants
  • polychlorinated-biphenyls
  • hydroxylated metabolites
  • competitive interactions
  • human transthyretin
  • binding globulin
  • expression
  • chemicals
  • protein

Fingerprint Dive into the research topics of 'Thyroid hormone receptor isoform selectivity of thyroid hormone disrupting compounds quantified with an in vitro reporter gene assay'. Together they form a unique fingerprint.

  • Cite this