Abstract
The iodothyronine deiodinases activate (Type 1 and 2 deidoinases or DIO1 and DIO2) or inactivate (DIO1 and the Type 3 deiodinase or DIO3) thyroid hormone depending on which iodine is removed from the iodothyronine molecule. These enzymes are selenoproteins, containing the rare amino acid selenocysteine (Sec) in their active center. Sec insertion sequence binding protein 2, SECISBP2, is an important component of the selenoprotein synthesis machinery, and its binding to the Sec insertion sequence (SECIS) element is crucial for Sec incorporation at the UGA codon to override termination. In patients with impaired selenoprotein synthesis due to SECISBP2 mutations, abnormal serum thyroid hormone profiles due to alterations in deiodinase activity are found. The deiodinase enzymes can also play important roles in the modulation of T3 within specific tissues. One example of this is the concerted regulation of Dio2 and Dio3 expression after muscle injury in mice which tightly controls intracellular T3 levels in muscle stem cells during muscle regeneration. Thus, expression of the deiodinase selenoproteins regulates both circulating and intracellular levels of active thyroid hormone independently of the hypothalamic-pituitary axis with significant physiologic consequences.
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Supported by NIDDK grant 44128, and grants from the Osher Center for Integrative Medicine and the Brigham Research Institute Fund to Maintain Research Excellence.
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Marsili, A., Larsen, P.R., Zavacki, A.M. (2016). Tissue-Specific Regulation of Thyroid Status by Selenodeiodinases. In: Hatfield, D., Schweizer, U., Tsuji, P., Gladyshev, V. (eds) Selenium. Springer, Cham. https://doi.org/10.1007/978-3-319-41283-2_41
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DOI: https://doi.org/10.1007/978-3-319-41283-2_41
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