Extranuclear Effects of Thyroid Hormones in Skeletal Muscle

Author(s): Sandra Incerpi , Paolo De Vito , Jens Z. Pedersen , Paolo Luly .

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)

Volume 11 , Issue 3 , 2011


The signals initiated by skeletal muscle contraction and exercise involve several biochemical mechanisms both in the short- and long-time range that are under the control of thyroid hormones as genomic as well as nongenomic mechanisms. The effect of thyroid hormones on skeletal muscle has been studied both in cells in culture and in vivo. In L- 6 myoblasts thyroid hormone increases intracellular calcium and pH. Administration of a single injection of thyroid hormone in rat i.p. leads to a rapid rise in T3 about 50-fold, that peaked at 2 hours. The effect of this treatment was evaluated on signaling kinases, in particular on the phosphorylation of the p38MAPK pathway, and AMP-activated protein kinase. Both were activated and both can be a downstream target of the integrin αvβ3, the reported plasma membrane receptor for thyroid hormones. Contractile activity leads to mitochondrial biogenesis within skeletal muscle, which gives rise to signaling pathways leading to the expression of transcription factors. These are activated by a Ca2+-dependent release, p38 and AMP-activated protein kinase. The activated transcription factors such as nuclear respiratory factor 1, interact with the coactivator PGC-1α to stimulate the expression of nuclear genes encoding mitochondrial proteins. This sequence of events can be induced not only by physical exercise, but also by thyroid hormone (T3) treatment in vivo, particularly in slow twitch skeletal muscle. In conclusion, the old statement that thyroid hormone helps to keep the steady state, is still valid, furthermore it contributes to a good performance of skeletal muscle as exercise does.

Keywords: AMP-activated protein kinase, glucose transport, integrin αvβ3, mitogen activated protein kinase, Na+/H+ exchanger, p38MAPK, peroxisome proliferator-activated receptor γ coactivator-1α, physical exercise, skeletal muscle, thyroid hormones

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Article Details

Year: 2011
Page: [188 - 198]
Pages: 11
DOI: 10.2174/187152211796642819
Price: $58

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