Abstract
The sodium iodide symporter (NIS) is the plasma membrane glycoprotein that mediates active iodide transport in the thyroid and other tissues, such as the salivary, gastric mucosa, rectal mucosa, bronchial mucosa, placenta and mammary glands. In the thyroid, NIS mediates the uptake and accumulation of iodine and its activity is crucial for the development of the central nervous system and disease prevention. Since the discovery of NIS in 1996, research has further shown that NIS functionality and iodine transport is dependent on the activity of the sodium potassium activated adenosine 5′-triphosphatase pump (Na+, K+-ATPase). In this article, I review the molecular mechanisms by which F inhibits NIS expression and functionality which in turn contributes to impaired iodide absorption, diminished iodide-concentrating ability and iodine deficiency disorders. I discuss how NIS expression and activity is inhibited by thyroglobulin (Tg), tumour necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β), interferon-γ (IFN-γ), insulin like growth factor 1 (IGF-1) and phosphoinositide 3-kinase (PI3K) and how fluoride upregulates expression and activity of these biomarkers. I further describe the crucial role of prolactin and megalin in regulation of NIS expression and iodine homeostasis and the effect of fluoride in down regulating prolactin and megalin expression. Among many other issues, I discuss the potential conflict between public health policies such as water fluoridation and its contribution to iodine deficiency, neurodevelopmental and pathological disorders. Further studies are warranted to examine these associations.
Highlights
Iodine is a vital micronutrient required at all stages of life; foetal life and early childhood being the most critical phases of requirement
I focus on the molecular mechanisms by which F inhibits Na+/I- symporter (NIS) functionality and gene expression. These findings provide unprecedented insights into the molecular mechanisms by which F inhibits iodine uptake, transport and reabsorption, and provide a basis for minimising or preventing the risk of adverse health outcomes associated with iodine deficiency
Diverse lines of evidence demonstrate that F inhibits NIS expression and functionality thereby contributing to impaired iodide absorption, diminished iodide-concentrating ability and iodine deficiency disorders
Summary
Iodine is a vital micronutrient required at all stages of life; foetal life and early childhood being the most critical phases of requirement. The authors reported that the thyroid gland of offspring of hypothyroid group exhibited histopathological changes as luminal obliteration of follicles, hyperplasia, fibroblastic proliferation and some degenerative changes [33] Taken together, these findings suggest that F induced maternal hypothyroidism may cause a number of biochemical disturbances in different brain regions of offspring that may lead to a pathophysiological state. F exposure result in higher risk of developmental disorders, including impaired cognitive function in children [34,35,36] Another experimental study found that excessive maternal exposure to F combined with a low iodine diet resulted in significantly increased oxidative stress in the brain of offspring compared to controls or animals exposed to F without iodine deficiency. These findings provide unprecedented insights into the molecular mechanisms by which F inhibits iodine uptake, transport and reabsorption, and provide a basis for minimising or preventing the risk of adverse health outcomes associated with iodine deficiency
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