The Thyroid Hormone Receptor-β-Selective Agonist GC-1 Differentially Affects Plasma Lipids and Cardiac Activity.
The Thyroid Hormone Receptor-β-Selective Agonist GC-1 Differentially Affects Plasma Lipids and Cardiac Activity.
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DOI：
10.1210/endo.141.9.7681
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发表时间：
2000-09
期刊：
影响因子：
4.8
通讯作者：
S. Trost;E. Swanson;B. Gloss;D. B. Wang-Iverson;Hongjiang Zhang;T. Volodarsky;Gary J Grover;
中科院分区：
文献类型：
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作者：
S. Trost;E. Swanson;B. Gloss;D. B. Wang-Iverson;Hongjiang Zhang;T. Volodarsky;Gary J Grover;
甲状腺激素影响许多器官的功能，并通过两种类型的甲状腺激素受体TRα和TRβ介导其不同的作用。关于优先与两种不同TR亚型相互作用的配体的作用知之甚少。在本研究中，在甲状腺功能减退小鼠中比较了等摩尔剂量的新型合成TRβ选择性化合物GC-1与T3的作用，结果表明GC-1具有比T3更好的降胆固醇作用和相似的降胆固醇作用。T3，而不是GC-1，增加心率和升高的信使RNA水平编码的If通道（HCN 2），心脏起搏器，在甲状腺功能减退的小鼠减少。T3具有比GC-1更大的正性肌力作用。T3（而非GC-1）使心脏和体重以及肌球蛋白重链α和β以及肌浆网腺苷三磷酸酶（Serca 2）的信使RNA正常化。在高脂血症大鼠中的额外剂量反应研究证实了GC-1对TRβ介导的参数的优先作用。
Thyroid hormones influence the function of many organs and mediate their diverse actions through two types of thyroid hormone receptors, TRα and TRβ. Little is known about effects of ligands that preferentially interact with the two different TR subtypes. In the current study the comparison of the effects of the novel synthetic TRβ-selective compound GC-1 with T3 at equimolar doses in hypothyroid mice revealed that GC-1 had better triglyceride-lowering and similar cholesterol-lowering effects than T3. T3, but not GC-1, increased heart rate and elevated messenger RNA levels coding for the If channel (HCN2), a cardiac pacemaker that was decreased in hypothyroid mice. T3 had a larger positive inotropic effect than GC-1. T3, but not GC-1, normalized heart and body weights and messenger RNAs of myosin heavy chain α and β and the sarcoplasmic reticulum adenosine triphosphatase (Serca2). Additional dose-response studies in hypercholesteremic rats confirmed the preferential effect of GC-1 on TRβ-mediated paramete...