Thyroid hormones and skeletal muscle — new insights and potential implications

Thyroid hormone signalling regulates crucial biological functions, including energy expenditure, thermogenesis, development and growth. The skeletal muscle is a major target of thyroid hormone signalling. The type two (DIO2) and three (DIO3) iodothyronine deiodinases have been identified in skeletal muscle. DIO2 expression is tightly regulated and catalyzes outer ring monodeiodination of the secreted prohormone tetraiodothyronine (T(4)) to generate the active hormone triiodothyronine (T(3)). T(3) may remain in the myocyte to signal through nuclear receptors or exit the cell to mix with the extracellular pool. By contrast, DIO3 inactivates T(3) through removal of an inner ring iodine. Regulation of the expression and activity of deiodinases constitutes a cell-autonomous, pre-receptor mechanism for controlling the intracellular concentration of T(3). This local control of T(3) activity is crucial during the various phases of myogenesis. Here, we review the roles of T3 in skeletal muscle development and homeostasis, with a focus on the emerging local deiodinase-mediated control of T3 signalling. Moreover, we discuss these novel findings in the context of both muscle homeostasis and pathology, and examine how they can be therapeutically harnessed to improve satellite cell-mediated muscle repair in patients with skeletal muscle disorders, muscle atrophy or injury