Haddad F, Qin A X, McCue S A, Baldwin K M
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA.
Am J Physiol. 1998 Jun;274(6):E1018-26. doi: 10.1152/ajpendo.1998.274.6.E1018.
This study examined nuclear thyroid receptor (TR) maximum binding capacity (Bmax), dissociation constant (Kd), and TR isoform (alpha1, alpha2, beta1) mRNA expression in rodent cardiac, "fast-twitch white," "fast-twitch red," and "slow-twitch red" muscle types as a function of thyroid state. These analyses were performed in the context of slow-twitch type I myosin heavy-chain (MHC) expression, a 3,5,3'-triiodothyronine (T3)-regulated gene that displays varying responsiveness to T3 in the above tissues. Nuclear T3 binding analyses show that the skeletal muscle types express more TRs per unit DNA than cardiac muscle, whereas the latter has a lower Kd than the former. Altered thyroid state had little effect on either cardiac Bmax or Kd, whereas hypothyroidism increased Bmax in the skeletal muscle types without affecting its Kd. Cardiac muscle demonstrated the greatest mRNA signal of TR-beta1 compared with the other muscle types, whereas the TR-alpha1 mRNA signals were more abundant in the skeletal muscle types, especially fast-twitch red. Hyperthyroidism increased the ratio of beta1 to alpha1 and decreased the ratio of alpha2- to alpha1+beta1-mRNA signal across the muscle types, whereas hypothyroidism caused the opposite effects. The nuclear T3 affinity correlated significantly with the TR-beta1 mRNA expression but not with TR-alpha1 mRNA expression. Collectively, these findings suggest that, despite a divergent pattern of TR mRNA expression in the different muscle types, these patterns follow similar qualitative changes under altered thyroid state. Furthermore, TR expression pattern cannot account for the quantitative and qualitative changes in type I MHC expression that occur in the different muscle types.
本研究检测了啮齿动物心脏、“快缩白肌”、“快缩红肌”和“慢缩红肌”等肌肉类型中甲状腺核受体（TR）的最大结合容量（Bmax）、解离常数（Kd）以及TR亚型（α1、α2、β1）的mRNA表达，作为甲状腺状态的函数。这些分析是在慢缩I型肌球蛋白重链（MHC）表达的背景下进行的，MHC是一种受3,5,3'-三碘甲状腺原氨酸（T3）调节的基因，在上述组织中对T3表现出不同的反应性。核T3结合分析表明，每单位DNA中骨骼肌类型表达的TR比心肌多，而心肌的Kd比骨骼肌低。甲状腺状态的改变对心脏的Bmax或Kd影响不大，而甲状腺功能减退会增加骨骼肌类型中的Bmax，而不影响其Kd。与其他肌肉类型相比，心肌显示出TR-β1的最大mRNA信号，而TR-α1的mRNA信号在骨骼肌类型中更丰富，尤其是快缩红肌。甲状腺功能亢进增加了β1与α1的比例，并降低了所有肌肉类型中α2与α1+β1 mRNA信号的比例，而甲状腺功能减退则产生相反的效果。核T3亲和力与TR-β1 mRNA表达显著相关，但与TR-α1 mRNA表达无关。总的来说，这些发现表明，尽管不同肌肉类型中TR mRNA表达模式不同，但在甲状腺状态改变时，这些模式遵循相似的定性变化。此外，TR表达模式不能解释不同肌肉类型中I型MHC表达的定量和定性变化。
