Developmental Exposure to Polychlorinated Biphenyls Exerts Thyroid Hormone-Like Effects on the Expression of RC3/Neurogranin and Myelin Basic Protein Messenger Ribonucleic Acids in the Developing Rat Brain1
Open accessAbstract
Polychlorinated biphenyls (PCBs) are a class of industrial compounds consisting of paired phenyl rings with various degrees of chlorination. They are now ubiquitous, persistent environmental contaminants that are routinely found in samples of human and animal tissues and are known to affect brain development. The effects of PCBs on brain development may be attributable, at least in part, to their ability to reduce circulating levels of thyroid hormone. However, the developmental effects of PCB exposure are not fully consistent with hypothyroidism. Because some individual PCB congeners interact strongly with various thyroid hormone binding proteins, several investigators have speculated that these congeners may be producing thyroid hormone-like effects on brain development. Therefore, we tested whether a mixture of PCBs, Aroclor 1254 (A1254), would produce an antithyroid or thyromimetic effect on the expression of known thyroid hormone-responsive genes in the developing brain. Pregnant female rats were fed various doses of A1254 (0, 1, 4, and 8 mg/kg) from gestational day 6 to weaning on postnatal day (P) 21. Pups derived from these dams were sampled on P5, P15, and P30. Total T4 was reduced by A1254 in a dose-dependent manner, but body weight of the pups or dams was not affected. The expression of RC3/Neurogranin and myelin basic protein was not affected by A1254 on P5 or P30. However, on P15, RC3/Neurogranin was elevated by A1254 in a dose-dependent manner, and myelin basic protein expression followed this general pattern. These data clearly demonstrate that the developmental effects of PCB exposure are not simply a function of PCB-induced hypothyroidism.
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These receptor- and hormone-dependent disturbances are functionally reflected in electrophysiological deficits, including reduced hippocampal and dentate gyrus LTP after developmental exposure to Aroclor 1254 or CB-77.
“These receptor- and hormone-dependent disturbances are functionally reflected in electrophysiological deficits, including reduced hippocampal and dentate gyrus LTP after developmental exposure to Aroclor 1254 or CB-77 (Gilbert and Crofton, 1999; Ogiue-Ikeda et al., 2008; Zoeller et al., 2000).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Zoeller et al., 2000
The Discussion reports that developmental Aroclor 1254 exposure reduced circulating thyroid hormone and altered thyroid hormone-responsive gene expression, supporting the hormone-related part of the claim. It does not report LTP measurements after Aroclor 1254 or CB-77 exposure; instead, the Discussion says the functional consequences of its findings are unclear. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPCBs reduce circulating thyroxine, interfere with hepatic and cerebral thyroid hormone metabolism, compete with T4 for binding to transthyretin, and can interact directly with thyroid hormone receptors, acting in a context-dependent agonistic or antagonistic manner.
“PCBs reduce circulating thyroxine, interfere with hepatic and cerebral thyroid hormone metabolism, compete with thyroxine (T4) for binding to transthyretin, and can interact directly with thyroid hormone receptors, acting in a context-dependent agonistic or antagonistic manner [a8] (Dsouki et al., 2024; Schug et al., 2015; Zoeller et al., 2000).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Zoeller et al., 2000
The Discussion (page unavailable) reports reduced circulating T4, and the introductory passage describes liver enzymes involved in thyroid-hormone metabolism and displacement of T4 from serum proteins. The Discussion also reports PCB-congener binding to transthyretin, but does not establish that this binding competes with T4. It presents altered brain deiodination and direct receptor-mediated agonist or antagonist action as possibilities, not established effects. (LLM, conf=0.86)
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Research works printed but not linked: 2
- Paxinos G, Watson C 1986 The rat brain in stereotaxic coordinates, ed 2. Academic Press, San Diego
- Schwartz HL 1983 Effect of thyroid hormone on growth and development. In: Oppenheimer JH, Samuels HH (eds) Molecular Basis of Thyroid Hormone Action. Academic Press, New York, pp 413-444
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“…disrupts cholinergic signaling through acetylcholinesterase inhibition which leads to the prolonged presence of acetylcholine in the synaptic cleft (Brown et al., 2007; Gilbert and Crofton, 1999; Jacobson and Jacobson, 1996; Lyu et al., 2020; Olasehinde and Olaniran, 2022; Zoeller et al., 2000).”
- Authors
- Zoeller, R. T., Dowling, A. L. S., & Vas, A. A.
- Affiliations
- University of Massachusetts Amherst (US)
- Corresponding author
- Zoeller, R. Thomas
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-01-01
- Volume
- 141
- Issue
- 1
- Pages
- 181-189
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2106883177
- Cited by
- 168
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 6 · 2014: 9 · 2013: 4 · 2012: 6
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Endocrinology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01es008333-03)
- National Institute of Mental Health
- National Institute of Environmental Health Sciences (ES-08333)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- polychlorinated biphenyls, Aroclor 1254, developmental neurotoxicity, thyroid hormones, myelin basic protein, thyroid hormone-responsive genes, brain development, hypothyroidism, prenatal exposure, total thyroxine, persistent pollutants
- MeSH terms
- Animals, Autoradiography, Body Weight, Brain, Calmodulin-Binding Proteins, Myelin Basic Protein, Female, Gene Expression Regulation, Nerve Tissue Proteins, Polychlorinated Biphenyls, Pregnancy, Radioimmunoassay, Receptors, Thyroid Hormone, RNA, Messenger, Thyroid Hormones, RNA Probes, Signal Transduction, Rats, Sprague-Dawley, In Situ Hybridization, Rats, Neurogranin
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