Adams G R, McCue S A, Zeng M, Baldwin K M
Department of Physiology and Biophysics, University of California Irvine, California 92697-4560, USA.
Am J Physiol. 1999 Apr;276(4 Pt 2):R954-61. doi: 10.1152/ajpregu.1999.276.4.r954.
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.
在出生后的时期，大鼠肢体肌肉通过用成年同种型替代胚胎（Emb）和新生（Neo）肌球蛋白重链（MHCs）来适应负重。我们的目的是根据骨骼肌中表达的六种MHC同种型来表征这种转变，并确定神经支配和甲状腺激素状态对成年MHC表型获得的重要性。通过注射丙硫氧嘧啶（PTU）使新生大鼠甲状腺功能减退。在正常和PTU亚组中，在15日龄时对腿部肌肉进行单侧去神经支配。在产后7、14、23和30天测定比目鱼肌（Sol）和跖肌（PLN）的MHC谱。在第7天，Sol的MHC谱为55%的I型、30%的Emb和10%的Neo；在PLN中，模式为60%的Neo和25%的Emb。到第30天，对照组中的Sol和PLN基本上达到了成年MHC谱。PTU增加了Sol中慢MHC的表达，而在PLN中，它通过保留新生MHC的表达显著抑制了IIb MHC。去神经支配减弱了PLN中IIb和Sol中I型的上调，并使模式转变为两种肌肉中IIa和IIx MHC的更大表达。与先前的观察结果相反，这些发现共同表明，完整的甲状腺和神经支配状态对于成年MHC表型的获得是必不可少的，特别是在快肌中。
