Skeletal Muscle Changes in Hypothyroidism

This chapter reviews hypothyroidism-induced structural and functional plasticity of motor units. Iodine deficiency and other alterations in iodine metabolism can lead to hypothyroidism. Motor unit and muscle fiber type classification is critical when considering plasticity. With hypothyroidism, motoneurons display decreased soma and axon diameter, which may increase their excitability and reduce conduction velocity. Neuromuscular junctions at type I and IIa fibers display reduced size and complexity (classification based on myosin heavy chain (MHC) expression), which improves their ability to maintain neuromuscular transmission. The cross-sectional area (CSA) of type I and IIa fibers is either maintained or increased, whereas that of type IIx and/or type IIb fibers decreases. Expression of MHC isoforms is altered in hypothyroid muscles, with increased expression of MHC_???? and reduced expression of MHC_?? and MHC_??. In fact, MHC content per half-sarcomere decreases at fibers expressing MHC_?? and/or MHC_??, reflecting fewer myosin cross-bridges available for force generation. Taken together, these changes result in reduced maximum force. The force generated per myosin cross-bridge is maintained, indicating that hypothyroidism does not impair cross-bridge force generation. Across fiber types, myosin cross-bridge cycling rates are reduced, as reflected by the markedly slower maximum velocity of shortening, rate constant for force redevelopment and ATP consumption rates.