Does 2,2′,4,4′-tetrabromodiphenyl ether interact directly with thyroid receptor?

• Published in: Journal of applied toxicology Vol. 31; no. 2; pp. 179 - 184
• Main Authors: Suvorov, Alexander, Bissonnette, Cyntia, Takser, Larissa, Langlois, Marie-France
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2011; Wiley; Wiley Subscription Services, Inc
• Subjects: Animals; Biological and medical sciences; Endocrine Disruptors - metabolism; Endocrine Disruptors - toxicity; Environmental Pollutants - metabolism; Environmental Pollutants - toxicity; environmental toxicology; Female; Flame Retardants - metabolism; Flame Retardants - toxicity; Frontal Lobe - drug effects; Frontal Lobe - metabolism; gene expression; Gene Expression Profiling; Gene Expression Regulation, Developmental - drug effects; Genes, Reporter; Halogenated Diphenyl Ethers - metabolism; Halogenated Diphenyl Ethers - toxicity; HEK293 Cells; Humans; Lactation; Liver - drug effects; Liver - metabolism; Male; Maternal Exposure; Medical sciences; microarrays; PBDE; Polybrominated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Rats; Response Elements - drug effects; thyroid hormone receptor; Thyroid Hormone Receptors beta - genetics; Thyroid Hormone Receptors beta - metabolism; thyroid hormone response element; Toxicology; Endocrine gland; Ether; thyroid hormone response element; DNA chip; Thyroid gland; Gene expression; Response element; microarrays; Toxicology; thyroid hormone receptor; PBDE; Environment; Thyroid hormone; environmental toxicology; Biological receptor; Hormonal receptor
• ISSN: 0260-437X; 1099-1263; 1099-1263
• DOI: 10.1002/jat.1580

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 [125I]T3 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. 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. 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 mechanisms.