Shao Y, Ojamaa K, Klein I, Ismail-Beigi F
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4951, USA.
Thyroid. 2000 Sep;10(9):753-9. doi: 10.1089/thy.2000.10.753.
Regulation of myocardial Na, K-ATPase gene expression by thyroid hormone was investigated in the heterotopically transplanted rat heart to distinguish the direct effects of the hormone on the heart from effects secondary to increased hemodynamic workload. In this model, the transplanted heart is histologically normal and spontaneously beating, but hemodynamically unloaded. Three days after transplantation, relative contents of ventricular Na, K-ATPase alpha2- and beta1-mRNAs and alpha1- and alpha2-proteins were increased twofold to threefold in the transplanted heart, but these changes were transient. We next determined the maximal triiodothyronine (T3)-induced changes that are observed in various parameters of Na, K-ATPase expression in the heart: treatment of nontransplanted euthyroid rats with T3 to reach hyperthyroid steady state resulted in significant increases in heart weight, RNA and RNA/protein ratio, Na, K-ATPase activity, Na, K-ATPase alpha2-protein and enzyme activity, and approximately threefold increase in both alpha2- and beta1-mRNA content. The effect of treatment with thyroxine (T4) on the heterotopically transplanted and the in situ heart was then examined. T4 treatment (of the host) resulted in a significant increase in Na, K-ATPase alpha1-, alpha2-, and beta1-mRNAs in transplanted hearts (1.6 +/- 0.1-, 2.4 +/- 0.2-, and 1.7 +/- 0.1-fold, respectively), that was associated with a 2.2 +/- 0.2-fold increase in alpha2 protein as compared to transplanted hearts in diluent-treated euthyroid hosts (p < 0.05 for all changes). In addition, T4-induced increments in transplanted hearts were similar to those observed in the corresponding in situ hearts of host rats treated with T4. We conclude that the increase in Na, K-ATPase expression by thyroid hormone largely occurs independently of increased cardiac work elicited by the hormone and reflects a direct action of the hormone on Na, K-ATPase gene expression.
为了区分甲状腺激素对心脏的直接作用与血流动力学负荷增加继发的作用，在异位移植的大鼠心脏中研究了甲状腺激素对心肌钠钾ATP酶基因表达的调节。在这个模型中，移植的心脏组织学正常且能自发跳动，但血流动力学上无负荷。移植后三天，移植心脏中室钠钾ATP酶α2和β1 mRNA以及α1和α2蛋白的相对含量增加了两倍至三倍，但这些变化是短暂的。接下来，我们确定了在心脏钠钾ATP酶表达的各种参数中观察到的最大三碘甲状腺原氨酸（T3）诱导的变化：用T3处理未移植的甲状腺功能正常的大鼠以达到甲状腺功能亢进稳态，导致心脏重量、RNA和RNA/蛋白比值、钠钾ATP酶活性、钠钾ATP酶α2蛋白和酶活性显著增加，并且α2和β1 mRNA含量增加约三倍。然后检查了用甲状腺素（T4）处理对异位移植心脏和原位心脏的影响。（对宿主）T4处理导致移植心脏中钠钾ATP酶α1、α2和β1 mRNA显著增加（分别为1.6±0.1倍、2.4±0.2倍和1.7±0.1倍），与用稀释剂处理的甲状腺功能正常宿主的移植心脏相比，α2蛋白增加了2.2±0.2倍（所有变化p<0.05）。此外，T4诱导的移植心脏中的增加与在用T4处理的宿主大鼠相应的原位心脏中观察到的增加相似。我们得出结论，甲状腺激素引起的钠钾ATP酶表达增加在很大程度上独立于激素引起的心脏工作增加，并且反映了激素对钠钾ATP酶基因表达的直接作用。
