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Does 2,2′,4,4′‐tetrabromodiphenyl ether interact directly with thyroid receptor?
Author(s) -
Suvorov Alexander,
Bissonnette Cyntia,
Takser Larissa,
Langlois MarieFrance
Publication year - 2011
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1580
Subject(s) - thyroid , thyroid hormone receptor , ether , endocrinology , in vitro , medicine , chemistry , gene , receptor , offspring , reporter gene , gene expression , biology , biochemistry , genetics , organic chemistry , pregnancy
2,2′,4,4′‐tetrabromodiphenyl Ether (BDE‐47) is a flame‐retardant chemical appearing at increasing concentrations and frequency in the environment and human samples. A number of health effects of exposure to BDE‐47 have been observed, thyroid disruption being the most sensitive. Our objective was to examine BDE‐47 interaction with thyroid receptor beta (TRβ). We used a variety of approaches, including in vitro binding assays, luciferase reporter‐gene transcriptional assays, and analysis of expression of thyroid responsive genes in rat offspring exposed perinatally to BDE‐47. We found that BDE‐47 alone or in mixture with 2,2′,4,4′,5‐pentabromodiphenyl ether (BDE‐99), 2,2′,4,4′,6‐pentabromodiphenyl ether (BDE‐100), and 2,2′,4,4′,5,5′‐hexabromodiphenyl ether (BDE‐153) does not compete with [ 125 I]T 3 for TRβ‐binding even at 4000 fold higher concentrations. Also, BDE‐47 does not affect thyroid responsive genes through TRβ in in vitro studies of transcription regulation. A subset of thyroid responsive genes were significantly differentially expressed in liver and frontal lobe brain samples of exposed pups, however, the action of BDE‐47 was neither agonistic or antagonistic to that of thyroid hormone. We conclude that BDE‐47 does not interact directly with TRβ1 nor does it influence its transcriptional activity. Developmental exposure of rats to BDE‐47 leads to differential expression of thyroid responsive genes in liver and brain due to unknown mechanism. Copyright © 2010 John Wiley & Sons, Ltd.