Possible mechanisms of thyroid hormone disruption in mice by BDE 47, a major polybrominated diphenyl ether congener.

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Yet another think that brominated compounds can do to screw up the

thyroid

Toxicol Appl Pharmacol. 2008 Feb 1;226(3):244-50. Epub 2007 Sep 22.

Possible mechanisms of thyroid hormone disruption in mice by BDE 47,

a major polybrominated diphenyl ether congener.

VM, Staskal DF, Ross DG, Diliberto JJ, DeVito MJ, Birnbaum

LS.

Polybrominated diphenyl ethers (PBDEs) are a class of polyhalogenated

aromatic compounds commercially used as fire retardants in consumer

products. These compounds have been shown to decrease thyroid hormone

concentrations in rodents after acute exposures. This study examines

the ability of 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) to

decrease circulating thyroid hormone concentrations and pairs this

with BDE 47-induced effects on genes involved in thyroid hormone

homeostasis. Female C57BL/6 mice (9 weeks old) were orally

administered 3, 10, or 100 mg/kg/day of BDE 47 for 4 days. Animals

were euthanized 24 h after the final dose (day 5) and liver, kidney,

and serum were collected for analysis. BDE 47 caused a significant

43% decrease at 100 mg/kg/day in serum total thyroxine (T(4))

concentrations. There was no increase in hepatic T(4)-glucuronidation

activity, but significant increases in hepatic Ugt1a1, Ugt1a7, and

Ugt2b5 mRNA expression accompany significant decreases in T(4)

concentrations at 100 mg/kg/day of BDE 47. Induction of PROD activity

occurred at the lowest dose (3 mg/kg/day). Cyp2b10 mRNA expression

also increased significantly at 10 and 100 mg/kg/day. These key

findings show that BDE activates the nuclear receptor, CAR. Decreases

in Mdr1a mRNA expression also occurred at the lowest dose

administered (3 mg/kg/day BDE 47). BDE 47 exposure also decreased

hepatic transthyretin and monocarboxylate transporter 8 (Mct8) mRNA

expression, suggesting that while induction of UGTs may be partly

responsible for T(4) decreases, other mechanisms are also involved.

No effects were seen in the kidney. We conclude that changes in

hepatic UGTs and transporters may be involved in decreases in

circulating T(4) following BDE 47 exposure.