The thyroid hormone plays a fundamental role in the development, growth, and metabolic homeostasis in all vertebrates by affecting the ex- pression of different sets of genes. A group of thioredoxin fold-containing selenoproteins known as deiodinases control thyroid hormone action by acti- vating or inactivating the precursor molecule thyro- xine that is secreted by the thyroid gland. These pathways ensure regulation of the availability of the biologically active molecule T3, which occurs in a time- and tissue-specific fashion. In addition, because cells and plasma are in equilibrium and deiodination
affects central thyroid hormone regulation, these local deiodinase-mediated events can also affect systemic thyroid hormone economy, such as in the case of non- thyroidal illness. Heightened interest in the field has been generated following the discovery that the deiodinases can be a component in both the Sonic hedgehog signaling pathway and the TGR-5 signaling cascade, a G-protein-coupled receptor for bile acids. These new mechanisms involved in deiodinase regu- lation indicate that local thyroid hormone activation and inactivation play a much broader role than previously thought.

Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences.

BB. Gereben, A. Zeçlda, M. Dentice, D. Salvatore and A. C. Bianco. Cellular and Molecular Life Sciences. November 9, 2007. doi: 10.1007/s00018-007-7396-0

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