The effects of hyperthyroidism on muscular dystrophy in the mdx mouse: greater dystrophy in cardiac and soleus muscle.

Muscle damage and repair were studied in mdx mice treated with triiodothyronine (T3) for 14 days. Hindlimb and cardiac muscles were examined for the severity of dystrophy, the degree of muscle centronucleation, and fiber size. In control and mdx mice, cardiac hypertrophy and skeletal muscle atrophy were present after T3 treatment. Both cardiac and soleus (but not fast-twitch) muscles had larger, more frequent dystrophic lesions in T3-treated mdx mice, and mdx soleus had an increased area of new myotubes after T3. Skeletal myogenesis in mdx mice may have been delayed by excess T3, possibly related to the general reduction in staining for basic fibroblast growth factor in hyperthyroid mice. These are the first observations of a metabolic perturbation which worsens mdx dystrophy and possibly repair in a muscle-specific manner, and are likely related to T3-induced changes in myosin heavy chain expression, and to increased mechanical strain on dystrophin-deficient muscles.