Effects of manganese on thyroid hormone homeostasis: Potential links

O. P. Soldin, Michael Aschner

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Manganese (Mn) is an essential trace nutrient that is potentially toxic at high levels of exposure. As a constituent of numerous enzymes and a cofactor, manganese plays an important role in a number of physiologic processes in mammals. The manganese-containing enzyme, manganese superoxide dismutase (Mn-SOD), is the principal antioxidant enzyme which neutralizes the toxic effects of reactive oxygen species. Other manganese-containing enzymes include oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and glutamine synthetase. Environmental or occupational exposure to high levels of manganese can cause a neuropathy resembling idiopathic Parkinson's disease, commonly referred to as manganism. Manganism and Parkinson's disease are both characterized by motor deficits and damage to nuclei of the basal ganglia, particularly the substantia nigra, with altered dopamine (and its metabolites) contributing to these disorders. Dopamine, a major neurotransmitter plays a crucial role in the modulation of the cognitive function, working memory and/or attention of the prefrontal cortex and the hippocampus. Dopamine is also a known inhibitory modulator of thyroid stimulating hormone (TSH) secretion. The involvement of dopamine and dopaminergic receptors in neurodevelopment, as well as TSH modulation, led us to hypothesize that excessive manganese exposure may lead to adverse neurodevelopmental outcomes due to the disruption of thyroid homeostasis via the loss of dopaminergic control of TSH regulation of thyroid hormones. This disruption may alter thyroid hormone levels, resulting in some of the deficits associated with gestational exposure to manganese. While the effects of manganese in adult populations are relatively well documented, comprehensive data on its neurodevelopmental effects are sparse. Given the importance of this topic, we review the potential participation of thyroid hormone dyshomeostasis in the neurodevelopmental effects of manganese positing the hypotheses that manganese may directly or indirectly affect thyroid function by injuring the thyroid gland or dysregulating dopaminergic modulation of thyroid hormone synthesis.

Original languageEnglish (US)
Pages (from-to)951-956
Number of pages6
JournalNeuroToxicology
Volume28
Issue number5 SPEC. ISS.
DOIs
StatePublished - Sep 2007
Externally publishedYes

Fingerprint

Manganese
Thyroid Hormones
Homeostasis
Dopamine
Thyrotropin
Thyroid Gland
Poisons
Modulation
Enzymes
Parkinson Disease
Isomerases
Glutamate-Ammonia Ligase
Lyases
Mammals
Coenzymes
Environmental Exposure
Dopamine Receptors
Hydrolases
Substantia Nigra
Occupational Exposure

Keywords

  • Dopamine
  • Manganese
  • Neurodevelopment
  • Thyroid hormone

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Toxicology

Cite this

Effects of manganese on thyroid hormone homeostasis : Potential links. / Soldin, O. P.; Aschner, Michael.

In: NeuroToxicology, Vol. 28, No. 5 SPEC. ISS., 09.2007, p. 951-956.

Research output: Contribution to journalArticle

Soldin, O. P. ; Aschner, Michael. / Effects of manganese on thyroid hormone homeostasis : Potential links. In: NeuroToxicology. 2007 ; Vol. 28, No. 5 SPEC. ISS. pp. 951-956.
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AB - Manganese (Mn) is an essential trace nutrient that is potentially toxic at high levels of exposure. As a constituent of numerous enzymes and a cofactor, manganese plays an important role in a number of physiologic processes in mammals. The manganese-containing enzyme, manganese superoxide dismutase (Mn-SOD), is the principal antioxidant enzyme which neutralizes the toxic effects of reactive oxygen species. Other manganese-containing enzymes include oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and glutamine synthetase. Environmental or occupational exposure to high levels of manganese can cause a neuropathy resembling idiopathic Parkinson's disease, commonly referred to as manganism. Manganism and Parkinson's disease are both characterized by motor deficits and damage to nuclei of the basal ganglia, particularly the substantia nigra, with altered dopamine (and its metabolites) contributing to these disorders. Dopamine, a major neurotransmitter plays a crucial role in the modulation of the cognitive function, working memory and/or attention of the prefrontal cortex and the hippocampus. Dopamine is also a known inhibitory modulator of thyroid stimulating hormone (TSH) secretion. The involvement of dopamine and dopaminergic receptors in neurodevelopment, as well as TSH modulation, led us to hypothesize that excessive manganese exposure may lead to adverse neurodevelopmental outcomes due to the disruption of thyroid homeostasis via the loss of dopaminergic control of TSH regulation of thyroid hormones. This disruption may alter thyroid hormone levels, resulting in some of the deficits associated with gestational exposure to manganese. While the effects of manganese in adult populations are relatively well documented, comprehensive data on its neurodevelopmental effects are sparse. Given the importance of this topic, we review the potential participation of thyroid hormone dyshomeostasis in the neurodevelopmental effects of manganese positing the hypotheses that manganese may directly or indirectly affect thyroid function by injuring the thyroid gland or dysregulating dopaminergic modulation of thyroid hormone synthesis.

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