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, John Furlow

Research output: Contribution to journalArticle

41 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 TRα/β specific reporter gene assays. For this purpose, the effects of compounds on 3,3′,5-triiodothyronine (T3)-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 T3-like BDE-OH and diiodobiphenyl (DIB) increased T3-induced TRα-activation, but not T3-induced TRβ-activation. BDE28 (100 nM) did not act via TRα, 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.

Original languageEnglish (US)
Pages (from-to)302-307
Number of pages6
JournalEnvironmental Toxicology and Pharmacology
Volume23
Issue number3
DOIs
StatePublished - May 1 2007

Fingerprint

Thyroid Hormone Receptors
Thyroid Hormones
Reporter Genes
Halogenated Diphenyl Ethers
Assays
Protein Isoforms
Genes
Chemical activation
Cercopithecus aethiops
Triiodothyronine
Xenopus
Luciferases
Fibroblasts
Kidney
In Vitro Techniques
Testing

Keywords

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

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Toxicology

Cite this

Thyroid hormone receptor isoform selectivity of thyroid hormone disrupting compounds quantified with an in vitro reporter gene assay. / Schriks, Merijn; Roessig, Julie M.; Murk, Albertinka J.; Furlow, John.

In: Environmental Toxicology and Pharmacology, Vol. 23, No. 3, 01.05.2007, p. 302-307.

Research output: Contribution to journalArticle

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