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Time course of myosin heavy chain transitions in neonatal rats: importance of innervation and thyroid state
1Department of Physiology and Biophysics, University of California Irvine, California 92697-4560, USA.
Insights
Postnatal rat muscles develop adult myosin heavy chains (MHCs) for weight-bearing. Both thyroid hormone and innervation are essential for achieving this adult MHC phenotype, especially in fast-twitch muscles.
Area of Science:
- Muscle physiology
- Developmental biology
- Endocrinology
Background:
- Postnatal limb muscles undergo myosin heavy chain (MHC) transitions from embryonic (Emb) and neonatal (Neo) to adult isoforms.
- This adaptation is crucial for weight-bearing and functional maturation.
Purpose of the Study:
- To characterize the developmental transition of six MHC isoforms in rat limb muscles.
- To investigate the roles of innervation and thyroid hormone status in achieving the adult MHC phenotype.
Main Methods:
- Neonatal rats were made hypothyroid using propylthiouracil (PTU).
- Unilateral denervation of leg muscles was performed at 15 days postpartum.
- MHC profiles of plantaris (PLN) and soleus (Sol) muscles were analyzed at various postnatal ages (7, 14, 23, 30 days).
Main Results:
- Control muscles achieved adult MHC profiles by day 30.
- Hypothyroidism (PTU) augmented slow MHC in soleus but repressed IIb MHC in plantaris, retaining neonatal MHC.
- Denervation reduced Type I MHC in soleus and IIb MHC in plantaris, increasing IIa and IIx MHC expression in both muscles.
Conclusions:
- Both intact thyroid hormone status and innervation are obligatory for the normal attainment of the adult MHC phenotype.
- Fast-twitch muscles appear particularly dependent on these factors for proper MHC maturation.
Abstract:
During the postnatal period, rat limb muscles adapt to weight bearing via the replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) 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 propylthiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were unilaterally denervated at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postpartum. 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 augmented slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upregulation 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 previous observations, these findings collectively suggest that both an intact thyroid and innervation state are obligatory for the attainment of the adult MHC phenotype, particularly in fast-twitch muscles.