Inhibition of the Biological Action of Thyroid Hormones by Actinomycin D and Puromycin
Inhibition of the Biological Action of Thyroid Hormones by Actinomycin D and Puromycin
复制标题
放线菌素D和嘌呤霉素抑制甲状腺激素的生物学作用
作者：
J. R. Tata
甲状腺激素引起的基础代谢率的刺激通常归因于激素和线粒体之间的直接相互作用改变了氧化磷酸化的效率。我们最近表明，当少量施用时，甲状腺激素会导致微粒体和线粒体的蛋白质合成速率早期显着增加，而不会产生前面描述的对线粒体功能的任何直接影响•••。因此，我们认为甲状腺激素的生热作用和促生长作用（也可能还有其他多种生物作用）都是影响蛋白质合成速率的细胞水平主要作用的次要表现。我最近获得了支持这一建议的进一步证据。研究表明，放线菌素 D 通过抑制信使 RNA 的形成来抑制蛋白质合成（参考文献 4），而嘌呤霉素抑制则发生在核糖体上新蛋白质的组装阶段。饥饿通过剥夺必需氨基酸的合成机制以及降低细胞中的RNA水平来抑制蛋白质合成8•已测量了每种抑制剂对甲状腺激素、L-甲状腺素和3,5,3'-三碘·L·甲状腺氨酸的生理反应的影响。结果表明，刺激蛋白质合成是对甲状腺激素产生全面生理反应的基本要求，并且激素对线粒体呼吸和磷酸化的直接作用并不能充分解释施用激素后观察到的基础代谢率增加。尤其是放线菌素 D 的作用还表明，甲状腺激素可能通过控制信使 RNA 的可用性而不是直接刺激蛋白质合成来发挥作用。
THE stimulation of basal metabolic rate induced by thyroid hormones has often been attributed to an alteration of the efficiency of oxidative phosphorylation by direct interaction between the hormone and mitochondrion1. It has recently been shown by us that, when administered in small amounts, thyroid hormones cause an early and substantial increase in the rate of protein synthesis by both microsomes and mitochondria, without any of the direct effects on mitochondrial function described earlier•·•. We suggested, therefore, that both the calorigenic and growth-promoting actions of thyroid hormones (and probably other multiple biological actions, as well) are secondary manifestations of a primary action at the cellular level which influences the rate of protein synthesis. I have recently obtained further evidence which supports this suggestion. It has been shown that actinomycin D inhibits protein synthesis by suppressing the formation of messenger RNA (ref. 4) whereas puromycin inhibition occurs at the stage of assembly of new protein at the ribosome•. Starvation suppresses protein synthesis by depriving the synthetic machinery of essential amino-acids as well as by lowering the level of RNA in the cell8• The effect of each of these inhibitory agents on the physiological response to the thyroid hormones, L-thyroxine and 3, 5, 3'-triiodo· L· thyronine, has been measured. The results indicate that stimulation of protein synthesis is an essential requirement for the full physiological response to thyroid hormone, and that direct action of hormone on mitochondrial respiration and phosphorylation is not an adequate explanation of the increased basal metabolic rate observed after administration of the hormones. The effect of actinomycin D in particular also suggests that thyroid hormones may act by controlling the availability of messenger RNA rather than by direct stimulation of protein synthesis.