Thyroidal dysfunction and environmental chemicals--potential impact on brain development.

Hdl Handle:
http://hdl.handle.net/10675.2/130
Title:
Thyroidal dysfunction and environmental chemicals--potential impact on brain development.
Authors:
Porterfield, S P
Abstract:
Certain polyhalogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs) and dibenzo-p-dioxins (dioxins, 2,3,7, 8-tetrachlorodibenzo-p-dioxin) have been shown to have neurotoxic effects and to alter thyroid function during critical periods of thyroid hormone-dependent brain development. This has led to the suggestion that some of the neurotoxic effects of these compounds could be mediated through the thyroid system. Thyroid hormones are essential for normal brain development during a critical period beginning in utero and extending through the first 2 years postpartum. They regulate neuronal proliferation, migration, and differentiation in discrete regions of the brain during definitive time periods. Even transient disruption of this normal pattern can impair brain development. Thyroid hormones are necessary for normal cytoskeletal assembly and stability and the cytoskeletal system is essential for migration and neuronal outgrowth. In addition, they regulate development of cholinergic and dopaminergic systems serving the cerebral cortex and hippocampus. Animals perinatally exposed to certain environmental organohalogens such as many of the PCBs and dioxins have abnormal thyroid function and neurologic impairment. Although there are both species and congener variabilities, most reports show exposure results in thyroid enlargement and reduced serum T(4) levels with normal T(3) levels. Initial research concentrated on studying the direct actions of xenobiotics on the thyroid; however, some of these compounds bear a structural resemblance to the natural thyroid hormones and have high affinity with thyroid hormone-binding proteins such as transthyretin. These compounds could act as agonists or antagonists for receptors of the thyroid/steroid/retinoic acid superfamily. These structurally similar organohalogens could act at multiple points to alter thyroid hormone action. The similarity of the neurologic impairment seen in thyroid disorders to that seen following PCB or dioxin exposure suggests that one mechanism of neurotoxicity of these compounds could involve interaction with the thyroid system.
Citation:
Environ Health Perspect. 2000 Jun; 108(Suppl 3):433-438
Issue Date:
23-Oct-2000
URI:
http://hdl.handle.net/10675.2/130
PubMed ID:
10852841
PubMed Central ID:
PMC1637839
Type:
Journal Article; Review
ISSN:
0091-6765
Appears in Collections:
Department of Physiology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorPorterfield, S Pen_US
dc.date.accessioned2010-09-24T22:03:24Z-
dc.date.available2010-09-24T22:03:24Z-
dc.date.issued2000-10-23en_US
dc.identifier.citationEnviron Health Perspect. 2000 Jun; 108(Suppl 3):433-438en_US
dc.identifier.issn0091-6765en_US
dc.identifier.pmid10852841en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/130-
dc.description.abstractCertain polyhalogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs) and dibenzo-p-dioxins (dioxins, 2,3,7, 8-tetrachlorodibenzo-p-dioxin) have been shown to have neurotoxic effects and to alter thyroid function during critical periods of thyroid hormone-dependent brain development. This has led to the suggestion that some of the neurotoxic effects of these compounds could be mediated through the thyroid system. Thyroid hormones are essential for normal brain development during a critical period beginning in utero and extending through the first 2 years postpartum. They regulate neuronal proliferation, migration, and differentiation in discrete regions of the brain during definitive time periods. Even transient disruption of this normal pattern can impair brain development. Thyroid hormones are necessary for normal cytoskeletal assembly and stability and the cytoskeletal system is essential for migration and neuronal outgrowth. In addition, they regulate development of cholinergic and dopaminergic systems serving the cerebral cortex and hippocampus. Animals perinatally exposed to certain environmental organohalogens such as many of the PCBs and dioxins have abnormal thyroid function and neurologic impairment. Although there are both species and congener variabilities, most reports show exposure results in thyroid enlargement and reduced serum T(4) levels with normal T(3) levels. Initial research concentrated on studying the direct actions of xenobiotics on the thyroid; however, some of these compounds bear a structural resemblance to the natural thyroid hormones and have high affinity with thyroid hormone-binding proteins such as transthyretin. These compounds could act as agonists or antagonists for receptors of the thyroid/steroid/retinoic acid superfamily. These structurally similar organohalogens could act at multiple points to alter thyroid hormone action. The similarity of the neurologic impairment seen in thyroid disorders to that seen following PCB or dioxin exposure suggests that one mechanism of neurotoxicity of these compounds could involve interaction with the thyroid system.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshBenzofurans / adverse effectsen_US
dc.subject.meshBrain / drug effects / growth & developmenten_US
dc.subject.meshEnvironmental Pollutants / adverse effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshPolychlorinated Biphenyls / adverse effectsen_US
dc.subject.meshThyroid Gland / drug effects / physiologyen_US
dc.subject.meshThyroid Hormones / pharmacologyen_US
dc.subject.meshXenobiotics / adverse effectsen_US
dc.titleThyroidal dysfunction and environmental chemicals--potential impact on brain development.en_US
dc.typeJournal Articleen_US
dc.typeReviewen_US
dc.identifier.pmcidPMC1637839en_US
dc.contributor.corporatenameDepartment of Physiologyen_US
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