Does 2,2',4,4'-tetrabromodiphenyl ether interact directly with thyroid receptor?
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.
Suvorov
Alexander
A
Département Pédiatrie, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Bissonnette
Cyntia
C
Takser
Larissa
L
Langlois
Marie-France
MF
D000818:Animals; D052244:Endocrine Disruptors / Q000378:metabolism* / Q000633:toxicity; D004785:Environmental Pollutants / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D005411:Flame Retardants / Q000378:metabolism* / Q000633:toxicity; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017930:Genes, Reporter; D057809:HEK293 Cells; D055768:Halogenated Diphenyl Ethers / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007774:Lactation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D011075:Polybrominated Biphenyls; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D020218:Response Elements / Q000187:drug effects; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*
D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; D037042:Thyroid Hormone Receptors beta; C511295:2,2',4,4'-tetrabromodiphenyl ether