Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors

Kelly J Gauger; Yoshihisa Kato; Koichi Haraguchi; Hans-Joachim Lehmler; Larry W Robertson; Ruby Bansal; R Thomas Zoeller

doi:10.1289/ehp.6672

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Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors

Journal article

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Peer reviewed

Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors

Kelly J Gauger, Yoshihisa Kato, Koichi Haraguchi, Hans-Joachim Lehmler, Larry W Robertson, Ruby Bansal and R Thomas Zoeller

Environmental health perspectives, Vol.112(5), pp.516-523

04/2004

DOI: 10.1289/ehp.6672

PMCID: PMC1241914

PMID: 15064154

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Abstract

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants routinely found in human and animal tissues. Developmental exposure to PCBs is associated with neuropsychologic deficits, which may be related to effects on thyroid hormone (TH) signaling in the developing brain. However, PCBs may interfere with TH signaling solely by reducing circulating levels of TH, or they may exert direct effects on TH receptors (TRs). Therefore, we tested whether maternal exposure to a commercial PCB mixture, Aroclor 1254 (A1254), exerts effects in the fetal brain by one or both of these mechanisms. Dams were dosed daily with 0, 1, or 4 mg/kg A1254 from gestational day 6 (GD6) until they were sacrificed on GD16. A1254 significantly reduced circulating levels of triiodothyronine (T3) and thyroxine (T4) in pregnant rats but increased the expression of several TH-responsive genes in the fetal cortex, including neuroendocrine-specific protein A (NSP-A), RC3/neurogranin, and Oct-1. These findings are consistent with a direct action of PCBs on TRs. However, we did not identify parent PCB congeners or metabolites that bound to rat TRs isolated from hepatic nuclei. These findings indicate that PCBs can interfere with TH signaling in the fetal brain by direct actions on the fetus rather than by producing maternal hypothyroidism.

Hypothyroidism - chemically induced

Hypothyroidism - metabolism

Brain - embryology

Fetus - metabolism

Male

Environmental Pollutants - metabolism

Cerebral Cortex - metabolism

Brain - metabolism

Triiodothyronine - metabolism

Female

Cerebral Cortex - drug effects

Polychlorinated Biphenyls - pharmacology

Liver - metabolism

Gene Expression Regulation, Developmental - drug effects

Environmental Pollutants - pharmacology

Rats

Polychlorinated Biphenyls - metabolism

Rats, Sprague-Dawley

Brain - drug effects

Chlorodiphenyl (54% Chlorine) - pharmacology

Fetus - drug effects

Pregnancy

Receptors, Thyroid Hormone - metabolism

Animals

Cerebral Cortex - embryology

Thyroid Hormones - metabolism

Thyroxine - metabolism

Details

Title: Subtitle: Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors
Creators: Kelly J Gauger - Biology Department, Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA 01003, USA
Yoshihisa Kato
Koichi Haraguchi
Hans-Joachim Lehmler
Larry W Robertson
Ruby Bansal
R Thomas Zoeller
Resource Type: Journal article
Publication Details: Environmental health perspectives, Vol.112(5), pp.516-523
DOI: 10.1289/ehp.6672
PMID: 15064154
PMCID: PMC1241914
NLM abbreviation: Environ Health Perspect
ISSN: 0091-6765
eISSN: 1552-9924
Publisher: United States
Grant note: P42 ES013661 / NIEHS NIH HHS P42 ES 07380 / NIEHS NIH HHS ES 10026 / NIEHS NIH HHS
Language: English
Date published: 04/2004
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute
Record Identifier: 9984001081202771

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