Time course of myosin heavy chain transitions in neonatal rats: importanceof innervation and thyroid state

During the postnatal period, rat limb muscles adapt to weight bearing via t he replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (M HCs) by the adult isoforms. Our aim was to characterize this transition in terms of the six MHC isoforms expressed in skeletal muscle and to determine the importance of innervation and thyroid hormone status on the attainment of the adult MHC phenotype. Neonatal rats were made hypothyroid via propyl thiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were u nilaterally denervated at 15 days of age. The MHC profiles of plantaris (PL N) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postp artum. At day 7, the Sol MHC profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC profile in the controls. PTU augmente d slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upreg ulation of IIb in the PLN and of Type I in the Sol and shifted the pattern to greater expression of IIa and IIx MHCs in both muscles. In contrast to p revious observations, these findings collectively suggest that both an inta ct thyroid and innervation state are obligatory for the attainment of the a dult MHC phenotype, particularly in fast-twitch muscles.