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

• Published in: Cellular and molecular life sciences : CMLS Vol. 65; no. 4; pp. 570 - 590
• Main Authors: Gereben, B, Zeöld, A, Dentice, M, Salvatore, D, Bianco, A. C
• Format: Journal Article
• Language: English
• Published: Basel Basel : SP Birkhäuser Verlag Basel 01.02.2008; Birkhäuser-Verlag; Springer Nature B.V
• Subjects: Animals; Antithyroid Agents - chemistry; Antithyroid Agents - pharmacology; bile acid; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain - enzymology; Cell Biology; Cell Membrane - enzymology; deiodinases; Endocrinology; Endoplasmic Reticulum - enzymology; Enzyme Activation; Enzymes; hormone metabolism; Hormones; Humans; Hypothyroidism - enzymology; Inactivation; Iodide Peroxidase - chemistry; Iodide Peroxidase - genetics; Iodide Peroxidase - metabolism; Kinetics; Life Sciences; Metabolism; Models, Molecular; Molecular biology; non-thyroidal illness syndrome; Obesity; Polymorphism, Single Nucleotide; Protein Conformation; Reference Values; Review; Sonic hedgehog pathway; Thyroid; Thyroid gland; Thyroid Hormones - physiology; bile acid; hormone metabolism; non-thyroidal illness syndrome; deiodinases; obesity; Thyroid; Sonic hedgehog pathway
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-007-7396-0

The thyroid hormone plays a fundamental role in the development, growth, and metabolic homeostasis in all vertebrates by affecting the expression of different sets of genes. A group of thioredoxin fold-containing selenoproteins known as deiodinases control thyroid hormone action by activating or inactivating the precursor molecule thyroxine 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 regulation indicate that local thyroid hormone activation and inactivation play a much broader role than previously thought.