Effects of manganese on thyroid hormone homeostasis: Potential links

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.

The placenta as a barrier for toxic and essential elements in paired maternal and cord blood samples of South African delivering women

“…47 At present, the risk of manganese-induced neurotoxicity during pre-and postnatal brain development, is not fully researched or understood. 48 The association between manganese uptake during pregnancy and early psychomotor development of children was reported. 49 Animal experimentation also show that neonatal rodents are at increased risk for manganese-induced neurotoxicity.…”

Relationship between serum zinc levels, thyroid hormones and thyroid volume following successful iodine supplementation

“…[15][16][17][18][19] Zinc is an essential trace metal for catalytic activities of many enzymes involved in the metabolism of hormones. Zinc effects on thyroid hormones are complex and include both synthesis and mode of action.…”

Oxidative Stress and Antioxidant Status in Hypo- and Hyperthyroidism

“…Varying forms of SOD (Mn-SOD, CuZn-SOD) present in the thyroid are the first line of defense in neutralizing ROS [188]. One study correlates several thyroid disorders to levels of CuZn-SOD and Mn-SOD, which are very high in malignant tumors [189].…”