The effects of thyroid hormone level and action in developing brain: Are these targets for the actions of polychlorinated biphenyls and dioxins?

Ellen S. Sher, Xiao-Ming Xu, Perrie M. Adams, Cheryl M. Craft, Stuart A. Stein

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Alterations in thyroid hormone level or responsivity to thyroid hormone have significant neurologic sequelae throughout the life cycle. During fetal and early neonatal periods, disorders of thyroid hormone may lead to the development of motor and cognitive disorders. During childhood and adult life, thyroid hormone is required for neuronal maintenance as well as normal metabolic function. Those with an underlying disorder of thyroid hormone homeostasis or mitochondrial function may be at greater risk for developing cognitive, motor, or metabolic dysfunction upon exposure to substances which alter thyroid hormone economy. Polychlorinated biphenyls (PCBs) and dioxins have been argued to interfere with thyroid hormone action and thus may affect the developing and mature brain. Animal models provide useful tools for studying the effects of thyroid hormone disorders and the effects of environmental endocrine disruptors. The congenitally hypothyroid, hyt/hyt, mouse exhibits abnormalities in both the cognitive and motor systems. In this mouse and other animal models of thyroid hormone disorders, delayed somatic and reflexive development are noted, as are permanent deficits in hearing and locomotor and adaptive motor behavior. This animal's behavioral abnormalities are predicated on anatomic abnormalities in the nervous system. In turn, these abnormalities are correlated with differences in neuronal structural proteins. In normal mice, the expression of mRNAs coding for these proteins occurs temporally with the onset of autonomous thyroid hormone production. The hyt/hyt mouse has a mutation in the thyroid stimulating hormone receptor (TSHr) gene which renders it incapable of transducing the TSH signal in the thyrocyte to produce thyroid hormone. Some behavioral and possibly some biochemical abnormalities in mice exposed to PCBs are similar to those seen in the hyt/hyt mouse. In addition to direct effects on brain development and neuronal maintenance, thyroid hormone is necessary for maintaining metabolic functioning through its influence on mitochondria. Because the brain is particularly sensitive to inadequate energy generation, disorders of thyroid hormone economy also indirectly impair brain functioning. Alteraltions in thyroid hormone level result in differing expression of mitochondrial genes. Mutations in these mitochondrial genes lead to well-recognized syndromes of encephalomyopathy, myopathy, and multisystem disorder. Hence, PCBs and dioxins, by possibly altering the thyroid hormone milieu, may alter the functioning of mitochondria in the generation of adenosine triphosphate (ATP). The use of animal models of thyroid hormone deficiency for behavioral, anatomic, histologic, and molecular comparison will help elucidate the mechanisms of action of these putative endocrine-disrupting compounds. The study of thyroid hormone disorders provides a template for relating thyroid hormone mediated effects on the brain to these compounds.

Original languageEnglish (US)
Pages (from-to)121-158
Number of pages38
JournalToxicology and Industrial Health
Volume14
Issue number1-2
StatePublished - Jan 1998
Externally publishedYes

Fingerprint

Dioxins
Polychlorinated Biphenyls
Thyroid Hormones
Brain
Animals
Mitochondria
Mitochondrial Genes
Animal Models
Genes
Maintenance
Nervous System Malformations
Endocrine Disruptors
Thyrotropin Receptors
Mutation
Psychological Adaptation
Audition
Neurology

Keywords

  • ATPase 6
  • Dioxins
  • Hypothyroidism
  • hyt/hyt mouse
  • Mitochondria
  • Mutation
  • Neurodevelopment
  • Polychlorinated biphenyls
  • Thyroid hormone
  • TSH receptor

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

The effects of thyroid hormone level and action in developing brain : Are these targets for the actions of polychlorinated biphenyls and dioxins? / Sher, Ellen S.; Xu, Xiao-Ming; Adams, Perrie M.; Craft, Cheryl M.; Stein, Stuart A.

In: Toxicology and Industrial Health, Vol. 14, No. 1-2, 01.1998, p. 121-158.

Research output: Contribution to journalArticle

@article{2445c85fbcd34100bfae68ed5038cd62,
title = "The effects of thyroid hormone level and action in developing brain: Are these targets for the actions of polychlorinated biphenyls and dioxins?",
abstract = "Alterations in thyroid hormone level or responsivity to thyroid hormone have significant neurologic sequelae throughout the life cycle. During fetal and early neonatal periods, disorders of thyroid hormone may lead to the development of motor and cognitive disorders. During childhood and adult life, thyroid hormone is required for neuronal maintenance as well as normal metabolic function. Those with an underlying disorder of thyroid hormone homeostasis or mitochondrial function may be at greater risk for developing cognitive, motor, or metabolic dysfunction upon exposure to substances which alter thyroid hormone economy. Polychlorinated biphenyls (PCBs) and dioxins have been argued to interfere with thyroid hormone action and thus may affect the developing and mature brain. Animal models provide useful tools for studying the effects of thyroid hormone disorders and the effects of environmental endocrine disruptors. The congenitally hypothyroid, hyt/hyt, mouse exhibits abnormalities in both the cognitive and motor systems. In this mouse and other animal models of thyroid hormone disorders, delayed somatic and reflexive development are noted, as are permanent deficits in hearing and locomotor and adaptive motor behavior. This animal's behavioral abnormalities are predicated on anatomic abnormalities in the nervous system. In turn, these abnormalities are correlated with differences in neuronal structural proteins. In normal mice, the expression of mRNAs coding for these proteins occurs temporally with the onset of autonomous thyroid hormone production. The hyt/hyt mouse has a mutation in the thyroid stimulating hormone receptor (TSHr) gene which renders it incapable of transducing the TSH signal in the thyrocyte to produce thyroid hormone. Some behavioral and possibly some biochemical abnormalities in mice exposed to PCBs are similar to those seen in the hyt/hyt mouse. In addition to direct effects on brain development and neuronal maintenance, thyroid hormone is necessary for maintaining metabolic functioning through its influence on mitochondria. Because the brain is particularly sensitive to inadequate energy generation, disorders of thyroid hormone economy also indirectly impair brain functioning. Alteraltions in thyroid hormone level result in differing expression of mitochondrial genes. Mutations in these mitochondrial genes lead to well-recognized syndromes of encephalomyopathy, myopathy, and multisystem disorder. Hence, PCBs and dioxins, by possibly altering the thyroid hormone milieu, may alter the functioning of mitochondria in the generation of adenosine triphosphate (ATP). The use of animal models of thyroid hormone deficiency for behavioral, anatomic, histologic, and molecular comparison will help elucidate the mechanisms of action of these putative endocrine-disrupting compounds. The study of thyroid hormone disorders provides a template for relating thyroid hormone mediated effects on the brain to these compounds.",
keywords = "ATPase 6, Dioxins, Hypothyroidism, hyt/hyt mouse, Mitochondria, Mutation, Neurodevelopment, Polychlorinated biphenyls, Thyroid hormone, TSH receptor",
author = "Sher, {Ellen S.} and Xiao-Ming Xu and Adams, {Perrie M.} and Craft, {Cheryl M.} and Stein, {Stuart A.}",
year = "1998",
month = "1",
language = "English (US)",
volume = "14",
pages = "121--158",
journal = "Toxicology and Industrial Health",
issn = "0748-2337",
publisher = "SAGE Publications Ltd",
number = "1-2",

}

TY - JOUR

T1 - The effects of thyroid hormone level and action in developing brain

T2 - Are these targets for the actions of polychlorinated biphenyls and dioxins?

AU - Sher, Ellen S.

AU - Xu, Xiao-Ming

AU - Adams, Perrie M.

AU - Craft, Cheryl M.

AU - Stein, Stuart A.

PY - 1998/1

Y1 - 1998/1

N2 - Alterations in thyroid hormone level or responsivity to thyroid hormone have significant neurologic sequelae throughout the life cycle. During fetal and early neonatal periods, disorders of thyroid hormone may lead to the development of motor and cognitive disorders. During childhood and adult life, thyroid hormone is required for neuronal maintenance as well as normal metabolic function. Those with an underlying disorder of thyroid hormone homeostasis or mitochondrial function may be at greater risk for developing cognitive, motor, or metabolic dysfunction upon exposure to substances which alter thyroid hormone economy. Polychlorinated biphenyls (PCBs) and dioxins have been argued to interfere with thyroid hormone action and thus may affect the developing and mature brain. Animal models provide useful tools for studying the effects of thyroid hormone disorders and the effects of environmental endocrine disruptors. The congenitally hypothyroid, hyt/hyt, mouse exhibits abnormalities in both the cognitive and motor systems. In this mouse and other animal models of thyroid hormone disorders, delayed somatic and reflexive development are noted, as are permanent deficits in hearing and locomotor and adaptive motor behavior. This animal's behavioral abnormalities are predicated on anatomic abnormalities in the nervous system. In turn, these abnormalities are correlated with differences in neuronal structural proteins. In normal mice, the expression of mRNAs coding for these proteins occurs temporally with the onset of autonomous thyroid hormone production. The hyt/hyt mouse has a mutation in the thyroid stimulating hormone receptor (TSHr) gene which renders it incapable of transducing the TSH signal in the thyrocyte to produce thyroid hormone. Some behavioral and possibly some biochemical abnormalities in mice exposed to PCBs are similar to those seen in the hyt/hyt mouse. In addition to direct effects on brain development and neuronal maintenance, thyroid hormone is necessary for maintaining metabolic functioning through its influence on mitochondria. Because the brain is particularly sensitive to inadequate energy generation, disorders of thyroid hormone economy also indirectly impair brain functioning. Alteraltions in thyroid hormone level result in differing expression of mitochondrial genes. Mutations in these mitochondrial genes lead to well-recognized syndromes of encephalomyopathy, myopathy, and multisystem disorder. Hence, PCBs and dioxins, by possibly altering the thyroid hormone milieu, may alter the functioning of mitochondria in the generation of adenosine triphosphate (ATP). The use of animal models of thyroid hormone deficiency for behavioral, anatomic, histologic, and molecular comparison will help elucidate the mechanisms of action of these putative endocrine-disrupting compounds. The study of thyroid hormone disorders provides a template for relating thyroid hormone mediated effects on the brain to these compounds.

AB - Alterations in thyroid hormone level or responsivity to thyroid hormone have significant neurologic sequelae throughout the life cycle. During fetal and early neonatal periods, disorders of thyroid hormone may lead to the development of motor and cognitive disorders. During childhood and adult life, thyroid hormone is required for neuronal maintenance as well as normal metabolic function. Those with an underlying disorder of thyroid hormone homeostasis or mitochondrial function may be at greater risk for developing cognitive, motor, or metabolic dysfunction upon exposure to substances which alter thyroid hormone economy. Polychlorinated biphenyls (PCBs) and dioxins have been argued to interfere with thyroid hormone action and thus may affect the developing and mature brain. Animal models provide useful tools for studying the effects of thyroid hormone disorders and the effects of environmental endocrine disruptors. The congenitally hypothyroid, hyt/hyt, mouse exhibits abnormalities in both the cognitive and motor systems. In this mouse and other animal models of thyroid hormone disorders, delayed somatic and reflexive development are noted, as are permanent deficits in hearing and locomotor and adaptive motor behavior. This animal's behavioral abnormalities are predicated on anatomic abnormalities in the nervous system. In turn, these abnormalities are correlated with differences in neuronal structural proteins. In normal mice, the expression of mRNAs coding for these proteins occurs temporally with the onset of autonomous thyroid hormone production. The hyt/hyt mouse has a mutation in the thyroid stimulating hormone receptor (TSHr) gene which renders it incapable of transducing the TSH signal in the thyrocyte to produce thyroid hormone. Some behavioral and possibly some biochemical abnormalities in mice exposed to PCBs are similar to those seen in the hyt/hyt mouse. In addition to direct effects on brain development and neuronal maintenance, thyroid hormone is necessary for maintaining metabolic functioning through its influence on mitochondria. Because the brain is particularly sensitive to inadequate energy generation, disorders of thyroid hormone economy also indirectly impair brain functioning. Alteraltions in thyroid hormone level result in differing expression of mitochondrial genes. Mutations in these mitochondrial genes lead to well-recognized syndromes of encephalomyopathy, myopathy, and multisystem disorder. Hence, PCBs and dioxins, by possibly altering the thyroid hormone milieu, may alter the functioning of mitochondria in the generation of adenosine triphosphate (ATP). The use of animal models of thyroid hormone deficiency for behavioral, anatomic, histologic, and molecular comparison will help elucidate the mechanisms of action of these putative endocrine-disrupting compounds. The study of thyroid hormone disorders provides a template for relating thyroid hormone mediated effects on the brain to these compounds.

KW - ATPase 6

KW - Dioxins

KW - Hypothyroidism

KW - hyt/hyt mouse

KW - Mitochondria

KW - Mutation

KW - Neurodevelopment

KW - Polychlorinated biphenyls

KW - Thyroid hormone

KW - TSH receptor

UR - http://www.scopus.com/inward/record.url?scp=6844240230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6844240230&partnerID=8YFLogxK

M3 - Article

C2 - 9460173

AN - SCOPUS:6844240230

VL - 14

SP - 121

EP - 158

JO - Toxicology and Industrial Health

JF - Toxicology and Industrial Health

SN - 0748-2337

IS - 1-2

ER -