Slow to fast muscle transformation following heterochronous isotransplantation is influenced by host thyroid hormone status.

We studied the effect of regeneration, altered innervation and thyroid hormone (TH) levels on fiber type transitions in slow soleus (SOL) muscles grafted (GRAFT) into host extensor digitorum longus (EDLh) muscles of euthyroid (EU), hyperthyroid (HT) and hypothyroid (HY) Lewis strain rats. SOL muscles were excised from 3-week to 4-week-old inbred Lewis rats and intramuscularly transplanted into EDLh muscles of 2-month-old female rats of the same strain. The proportions of type 1, 2A, 2X and 2B fibers of GRAFT were determined by immunohistochemistry and compared with those of EDLh muscle and EDL and SOL muscles of the unoperated contralateral hind limb. After an average regeneration period of 6-7 months and after being reinnervated by the "fast" peroneal nerve of EDLh muscle, GRAFT was transformed into a fast muscle. However, the extent of GRAFT transformation varied with different TH states. In the EU rats, GRAFT contained about 95 % of fast fibers, among which type 2X and 2B fibers predominated (about 75 %). The transition toward fast muscle phenotype was more pronounced in HT status, where the fastest type 2B fibers predominated. On the contrary, in HY status, the slow to fast transformation was less pronounced, as GRAFT contained less type 2B and 2X but more type 2A and 1 fibers. We conclude that the type of innervation is the crucial factor for the slow to fast fiber type transitions in GRAFT, but the extent of muscle transformation is further modulated by altered TH status.