1: Neurotoxicology. 2007 Sep;28(5):951-6. Epub 2007 May 13.

Effects of manganese on thyroid hormone homeostasis: potential links.

Soldin OP, Aschner M.

Department of Oncology and Medicine, The Center for Study of Sex Differences,
Georgetown University Medical Center, Washington, DC, USA. os35@georgetown.edu

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.

PMCID: PMC2067987
PMID: 17576015 [PubMed - indexed for MEDLINE]