Davis P J, Davis F B
Department of Medicine, Albany Medical College, New York 12208, USA.
Thyroid. 1996 Oct;6(5):497-504. doi: 10.1089/thy.1996.6.497.
Nongenomic actions of thyroid hormone are by definition independent of nuclear receptors for the hormone and have been described at the plasma membrane, various cell organelles, the cytoskeleton, and in cytoplasm. The actions include alterations in solute transport (Ca2+, Na+, glucose), changes in activities of several kinases, including protein kinase C, cAMP-dependent protein kinase and pyruvate kinase M2 (PKM2), effects on efficiency of specific mRNA translation and mRNA t1/2, modulation of mitochondrial respiration, and regulation of actin polymerization (promotion of formation of F-actin). Iodothyronines also can regulate nongenomically the state of contractile elements in vascular smooth muscle cells (VSMC). The physiologic significance at the cellular level of certain of these actions has been demonstrated, for example, in the cases of myocardiocyte Na+ current, red cell Ca2+ content, and the control by hormone-induced alterations in actin solubility of cell surface activity of iodothyronine 5'-monodeiodinase activity and the intracellular distribution of protein disulfide isomerase activity. The physiologic significance of these actions at the organ or system level is less clear, but extranuclear effects of thyroid hormone on myocardial Na+ channel, sarcoplasmic reticulum Ca(2+)-ATPase activity, and contractile state of VSMC may each contribute to acute effects of thyroid hormone on cardiac output that have recently been described clinically. The molecular mechanisms for nongenomic actions are incompletely understood; relevant binding sites and signal transduction pathways have been described for hormone actions on plasma membrane Ca(2+)-ATPase activity, and PKM2 monomer is known to bind T3 and, as a result, prevent activation of the kinase via tetramer formation. Nongenomic actions of thyroid hormone may have different structure-activity relationships of iodothyronines from those effects that depend upon nuclear receptors; they may have different time courses and may invoke complex signal transduction pathways before the action is detected.
从定义上来说，甲状腺激素的非基因组作用独立于该激素的核受体，并且已在质膜、各种细胞器、细胞骨架和细胞质中被描述。这些作用包括溶质转运（Ca2+、Na+、葡萄糖）的改变、几种激酶活性的变化，包括蛋白激酶C、环磷酸腺苷（cAMP）依赖性蛋白激酶和丙酮酸激酶M2（PKM2）、对特定mRNA翻译效率和mRNA半衰期的影响、线粒体呼吸的调节以及肌动蛋白聚合的调控（促进F-肌动蛋白的形成）。碘甲状腺原氨酸还可以非基因组方式调节血管平滑肌细胞（VSMC）中收缩元件的状态。这些作用中某些在细胞水平的生理意义已得到证实，例如，在心肌细胞Na+电流、红细胞Ca2+含量以及激素诱导的肌动蛋白溶解度改变对碘甲状腺原氨酸5'-单脱碘酶活性的细胞表面活性和蛋白质二硫键异构酶活性的细胞内分布的控制方面。这些作用在器官或系统水平的生理意义尚不清楚，但甲状腺激素对心肌Na+通道、肌浆网Ca(2+)-ATP酶活性和VSMC收缩状态的核外效应可能各自促成了最近临床描述的甲状腺激素对心输出量的急性影响。非基因组作用的分子机制尚未完全了解；已经描述了激素对质膜Ca(2+)-ATP酶活性作用的相关结合位点和信号转导途径，并且已知PKM2单体可结合T3，从而通过四聚体形成阻止激酶的激活。甲状腺激素的非基因组作用可能具有与依赖于核受体的效应不同的碘甲状腺原氨酸结构-活性关系；它们可能具有不同的时间进程，并且在检测到作用之前可能引发复杂的信号转导途径。
