Hyperthyroidism impairs early repair in normal but not dystrophic mdx mouse tibialis anterior muscle. An in vivo study.

The effect of hyperthyroidism on muscle repair was examined in mdx and control mice injected with triiodothyronine (T3) for 4 weeks. On day 24 of treatment, the right tibialis anterior (TA) muscle was crush-injured; 3 days later, mice received intraperitoneal [3H]thymidine to label newly synthesized DNA. One day later, muscles from both limbs were removed to study the severity of dystrophy (uncrushed muscle) and the regeneration response (crushed muscle). In uncrushed TA muscle, the area of active dystrophy (fiber damage and infiltration as a proportion of muscle cross-sectional area) was reduced by half after T3 treatment. Uncrushed muscle fiber diameter was lower in T3-treated control muscles. In crushed muscles, the diameter of new myotubes was larger in mdx mice than in controls and was reduced after T3 treatment in control regenerating muscle. In the same muscles, developmental myosin heavy chain was present in new myotubes and in small numbers of mononuclear cells (possibly differentiating myoblasts) near new myotubes and surviving fibers. Myotube density in the regenerating muscles was not changed by T3 treatment, although the number of myotube nuclei per field was decreased in control and increased in mdx T3-treated mice. Results extend previous reports of T3 effects on dystrophy and the strain difference in muscle precursor cell (mpc) proliferation. The results also suggest the hypothesis that excess T3 affects muscle regeneration either by reducing mpc proliferation or by increasing mpc fusion early in regeneration in control and mdx muscle.