METABOLIC EFFECTS OF THYROXINE IN VITRO
METABOLIC EFFECTS OF THYROXINE IN VITRO
复制标题
甲状腺素的体外代谢作用
DOI：
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发表时间：
1951
影响因子：
5.2
通讯作者：
G. Feldott
中科院分区：
文献类型：
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作者：
H. Lardy;G. Feldott
对甲状腺激素发挥代谢作用的机制的研究必须设计为获得与几个不同问题相关的信息。首先，有必要了解激素代谢活性形式的化学性质，并希望知道哪些结构修改可以在不丧失活性的情况下进行，哪些会导致完全丧失活性。其次，有必要了解激素在多大程度上影响原生质组织。最后一个问题是，这种影响到底是通过什么机制施加的？目前，生物化学家希望从荷尔蒙对酶催化反应的影响方面找到答案。Taurog和Chaikoffl以及Laidlaw*的研究使我们相信，甲状腺激素本身就是甲状腺激素的循环形式。目前尚不清楚甲状腺素在成为活性激素之前是否会在其影响的细胞内经历新陈代谢和结构变化。在没有完全消除激素活性的情况下，允许与甲状腺素的结构发生相当大的偏离。8 Neimann和他的同事4解释说，他们合成的甲状腺素异构体的生物活性表明，只有那些能够氧化成奎宁形式的结构才具有激素活性。这重新引起了人们对KendalP长期倡导的概念的兴趣：甲状腺激素参与氧化还原系统。关于证明激素的新陈代谢影响所需的组织水平，有相当多的数据可用。从动物身上取出的一些不同器官的耗氧率增加了，这些器官以前曾被给予相对大剂量的甲状腺素或甲状腺物质。这种反应在组织切片中仍然很明显，在一些情况下，已经被追踪到组织中某些酶含量的实际增加。在注射激素后，需要相当长的时间间隔才能观察到这种反应。当甲状腺激素直接应用于体外存活的组织时，得到的结果不太一致。举个例子，Davis、Da Costa和Hastings7发现，在切除的完整青蛙心脏中添加甲状腺素可以增加呼吸频率，但如果切开心脏则没有任何效果。一些工作人员80发现，极低浓度的甲状腺素可以加速肌肉碎块对亚甲基蓝的还原。关于甲状腺素促进粉碎组织耗氧量的报道相对较少，但似乎还没有得到证实。关于甲状腺素对酶系统的作用机制，我们的实验始于1942年，当时我们试图证实卡特的报告，即甲状腺素增加了兔精子的呼吸。我们发现，甲状腺激素对酶系统的作用机制尚不清楚。我们在这一领域的实验始于1942年，当时我们试图证实卡特的报告，即甲状腺素增加了兔精子的呼吸。我们发现，甲状腺激素对酶系统的作用机制尚不清楚
Studies of the mechanism by which the hormone of the thyroid gland exerts its metabolic effects must of necessity be designed to obtain information relevant to several different questions. First of all, it is necessary to learn the chemical nature of the metabolically active form of the hormone, and it is desirable to know which modifications of the structure can be made without loss of activity and which result in complete loss of activity. Secondly, it is necessary to learn the level of protoplasmic organization at which the hormone exerts its influence. The final question is, by what exact mechanism is the influence exerted? Biochemists, currently, want this answer in terms of effects of the hormone on enzymatically catalyzed reactions. The studies of Taurog and Chaikoffl and of Laidlaw* lead us to believe that thyroxine itself is the circulating form of the thyroid hormone. Whether thyroxine undergoes metabolic and structural changes within the cells it influences before it becomes the active hormone is still not known. Rather wide deviations from the structure of thyroxine are permissible without complete elimination of hormonal activity.8 Neimann and coworkers4 have interpreted the biological activitp of their synthetic isomers of thyroxine as indicating that only those structures capable of oxidation to a quinoid form have hormone activity. This renewed interest in the concept long championed by KendalP: that thyroxine participated in oxidationreduction systems. In regard to the level of organization required to demonstrate metabolic effects of the hormone, considerably more data are available. An increased rate of oxygen consumption has been observed in a number of different organs removed from animals which had previously been given relatively large large doses of thyroxine or thyroid substance. The response is still apparent in tissue slices and in several cases has been traced to an actual increase in the tissue content of certain enzymes. A considerable time interval is needed, following administration of the hormone, before such responses can be observed. When thyroxine is applied directly to surviving tissue in vitro, less consistent results are obtained. To cite an example, Davis, Da Costa, and Hastings7 found that the addition of thyroxine to excised, intact frog heart increased the rate of respiration, but if the heart was sliced no effect was obtained. Some workers80 have found extremely low concentrations of thyroxine to accelerate methylene blue reduction by minced muscle. The comparatively few reports of thyroxine accelerating oxygen consumption of minced tissue seem not to have been confirmed.'O As far as the mechanism of thyroxine's action on enzyme systems is concerned, everything remains to be discovered. Our experiments in this field began in 1942, when we attempted to confirm the report of Carter" that thyroxine increased the respiration of rabbit spermatozoa. We found that