Science Inventory

POSSIBLE MECHANISMS OF THYROID HORMONE DISRUPTION IN MICE BY BDE 47, A MAJOR POLYBROMINATED DIPHENYL ETHER CONGENER

Citation:

RICHARDSON, V., D. STASKAL, J. J. DILIBERTO, D. G. ROSS, M. J. DEVITO, AND L. S. BIRNBAUM. POSSIBLE MECHANISMS OF THYROID HORMONE DISRUPTION IN MICE BY BDE 47, A MAJOR POLYBROMINATED DIPHENYL ETHER CONGENER. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 226(3):244-250, (2008).

Impact/Purpose:

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

Description:

ABSTRACT Polybromindated 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. Based on their capacity to glucuronidate hormones and xenobiotics, UDP-glucuronosyltransferases (UGTs) play a key role in hormone homeostasis and xenobiotic detoxification. 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. 65-day old female C57BL/6 mice were orally administered 3, 10, or 100 mg/kg/day of BDE 47 for 4 days. Animals were euthanized 24 hours 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 (T4) concentrations. BDE 47 also caused a significant dose-related increase in Cyp2b10 and PROD, which is consistent with constitutive androstane receptor (CAR) activation. There was no increase in hepatic T4-glucuronidation activity, but significant increases in hepatic Ugt1a1, Ugt1a7, and Ugt2b5 mRNA expression accompany significant decreases in T4 concentrations at 100 mg/kg/day of BDE 47. BDE 47 exposures also decreased hepatic transthyretin and monocarboxylate transporter 8 (Mct8) mRNA expression, suggesting that induction of UGTs could in part be responsible for T4 decreases, but other mechanisms may also be involved. We conclude that UGTs as well as transporters may be involved in decreases in circulating T4 following BDE 47 exposure, and these effects may be mediated by activation of CAR.

URLs/Downloads:

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Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 02/01/2008
Record Last Revised: 10/15/2008
OMB Category: Other
Record ID: 164064

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

EXPERIMENTAL TOXICOLOGY DIVISION

IMMEDIATE OFFICE