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Selenium, selenoproteins and the thyroid gland: interactions in health and disease

Abstract

The trace element selenium is an essential micronutrient that is required for the biosynthesis of selenocysteine-containing selenoproteins. Most of the known selenoproteins are expressed in the thyroid gland, including some with still unknown functions. Among the well-characterized selenoproteins are the iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases, enzymes involved in thyroid hormone metabolism, regulation of redox state and protection from oxidative damage. Selenium content in selenium-sensitive tissues such as the liver, kidney or muscle and expression of nonessential selenoproteins, such as the glutathione peroxidases GPx1 and GPx3, is controlled by nutritional supply. The thyroid gland is, however, largely independent from dietary selenium intake and thyroid selenoproteins are preferentially expressed. As a consequence, no explicit effects on thyroid hormone profiles are observed in healthy individuals undergoing selenium supplementation. However, low selenium status correlates with risk of goiter and multiple nodules in European women. Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined. The baseline selenium status of an individual could constitute the most important parameter modifying the outcome of selenium supplementation, which might primarily disrupt self-amplifying cycles of the endocrine–immune system interface rectifying the interaction of lymphocytes with thyroid autoantigens. Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system–thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction.

Key Points

  • Selenium is needed for biosynthesis of selenoproteins, including thyroid hormone metabolizing enzymes (iodothyronine deiodinases), hydrogen peroxide degrading enzymes (glutathione peroxidases) and enzymes affecting endoplasmic reticulum function

  • Endogenous pathways ensure that the thyroid gland and thyroid selenoproteins are exceptionally well supplied with selenium and largely resistant to selenium deficiency

  • Selenium status declines and selenoprotein biosynthesis is impaired in inflammatory diseases, which potentially necessitates supplementation with this trace element

  • Selenium supplementation trials in patients with Hashimoto thyroiditis successfully reduced autoantibody concentrations and improved selenium status and quality of life

  • However, not all selenium supplementation trials have been successful and the underlying mechanisms of the selenium effects and the major parameters controlling trial outcome are unknown

  • Selenium supplementation is hypothesized to improve functioning of both thyrocytes and immune cells, thereby rectifying the derailed interaction of lymphocytes with thyroid autoantigens in selenium-deficient patients

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Figure 1: Pathways involved in thyroid peroxide generation (left) and selenium-dependent cell protection (right).

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Acknowledgements

The author expresses his gratitude to Drs Josef Köhrle, Ulrich Schweizer, Peter J. Hofmann, Birgit Hollenbach, Axel Schomburg and Jazmin Chiu-Ugalde for helpful discussions and critical remarks on the manuscript. Research in the author's laboratory is supported by the German Cancer Aid (Deutsche Krebshilfe, 10-1792 Scho2), Berlin-Brandenburg School for Regenerative Therapies (BSRT) and the Deutsche Forschungsgemeinschaft DFG (GraKo 1208/2, Scho 849/2-2).

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Schomburg, L. Selenium, selenoproteins and the thyroid gland: interactions in health and disease. Nat Rev Endocrinol 8, 160–171 (2012). https://doi.org/10.1038/nrendo.2011.174

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