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Complex regulation of thyroid hormone action: multiple opportunities for pharmacological intervention
Yun-Bo Shi1, James W A Ritchie, Peter M Taylor
1Unit on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, National Institutes of Child Health and Human Development, National Institute of Health, Building 18T, Room 106, Bethesda, MD 20892-5431, USA. shi@helix.nih.gov
Abstract:
The thyroid hormone (TH; 3,3',5,5'-tetra-iodothyronine and 3,3',5'-triiodothyronine) regulates growth, development, and critical metabolic functions. Thyroid diseases are among the most prevalent group of metabolic disorders in the Western world. TH exerts effects through complex biological pathways, which offer a wealth of opportunities to pharmacologically intervene in TH signalling at numerous steps. These include biosynthesis, cell-specific uptake or export (involving L-type amino acid transporter, organic anion transporter, organic cation transporter, or multidrug resistance transporter), as well as nuclear targeting and actions (the latter including TH receptor binding and histone acetylation/deacetylation). Such processes represent potentially important pharmacological targets for the design of novel or improved therapies for TH disorders, obesity, and cardiovascular diseases.