Dietary Exposure to 2,2',4,4'-Tetrabromodiphenyl Ether (PBDE-47) Alters Thyroid Status and Thyroid Hormone–Regulated Gene Transcription in the Pituitary and Brain

Lema, Sean C.; Dickey, Jon T.; Schultz, Irvin R.; Swanson, Penny

doi:10.1289/ehp.11570

Dietary Exposure to 2,2',4,4'-Tetrabromodiphenyl Ether (PBDE-47) Alters Thyroid Status and Thyroid Hormone–Regulated Gene Transcription in the Pituitary and Brain

Journal Article · Mon Dec 01 00:00:00 EST 2008 · Environmental Health Perspectives

DOI:https://doi.org/10.1289/ehp.11570· OSTI ID:1627108

Lema, Sean C. ^[1]; Dickey, Jon T. ^[2]; Schultz, Irvin R. ^[3]; Swanson, Penny ^[4]

National Oceanic and Atmospheric Administration (NOAA), Seattle, WA (United States); DOE/OSTI
University of Washington, Seattle, WA (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
National Oceanic and Atmospheric Administration (NOAA), Seattle, WA (United States)

Polybrominated diphenyl ether (PBDE) flame retardants have been implicated as disruptors of the hypothalamic-pituitary-thyroid axis. Animals exposed to PBDEs may show reduced plasma thyroid hormone (TH), but it is not known whether PBDEs impact TH-regulated pathways in target tissues. We examined the effects of dietary exposure to 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47)—commonly the highest concentrated PBDE in human tissues—on plasma TH levels and on gene transcripts for glycoprotein hormone α-subunit (GPHα) and thyrotropin β-subunit (TSHβ) in the pituitary gland, the autoinduced TH receptors α and β in the brain and liver, and the TH-responsive transcription factor basic transcription element-binding protein (BTEB) in the brain. Breeding pairs of adult fathead minnows (Pimephales promelas) were given dietary PBDE-47 at two doses (2.4 μg/pair/day or 12.3 μg/pair/day) for 21 days. Minnows exposed to PBDE-47 had depressed plasma thyroxine (T4), but not 3,5,3'-triiodothyronine (T3). This decline in T4 was accompanied by elevated mRNA levels for TStHβ (low dose only) in the pituitary. PBDE-47 intake elevated transcript for TH receptor αin the brain of females and decreased mRNA for TH receptor β in the brain of both sexes, without altering these transcripts in the liver. In males, PBDE-47 exposure also reduced brain transcripts for BTEB. Our results indicate that dietary exposure to PBDE-47 alters TH signaling at multiple levels of the hypothalamic-pituitary-thyroid axis and provide evidence that TH-responsive pathways in the brain may be particularly sensitive to disruption by PBDE flame retardants.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); West Coast Center for Oceans and Human Health (WCCOHH)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1627108

Journal Information:: Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: 12 Vol. 116; ISSN 0091-6765

Publisher:: National Institute of Environmental Health SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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Dietary Exposure to 2,2',4,4'-Tetrabromodiphenyl Ether (PBDE-47) Alters Thyroid Status and Thyroid Hormone–Regulated Gene Transcription in the Pituitary and Brain

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