从变温动物到恒温动物的转变：钠转运和甲状腺激素的可能作用。

Fed Proc. 1976 Aug;35(10):2180-4.

The evolutionary transition from poikilothermy to homeothermy required the recruitment of complex mechanisms that provided both higher rates of heat production and regulation of heat loss in the presence of wide variations in ambient temperature. Two pathways that have been considered to be contributors to the transition to homeothermy are thyroid-regulated thermogenesis and nonshivering thermogenesis in the adaptation to cold. These pathways may yield higher rates of heat production in homeotherms by two processes that need not be mutually exclusive: a) hydrolysis of ATP and consequent generation of the Pi acceptor--ADP, or b) decreased coupling of mitochondrial oxidative phosphorylation. A significant fraction of both thyroid and catecholamine thermogenesis has been ascribed to enhanced energy expenditure in active transmembrane Na+ transport (i.e., the Na+ pump). By extension these findings implicate the Na+ pump as a heat source in the evolution of the homeotherms. The thermogenic response to thyroid hormone is both rapid and profound in homeotherms (mammals), and more slowly evident and probably lesser in magnitude in poikilotherms (amphibia and reptiles). One crucial pathway in the evolution to homeothermy may be nonshivering thermogenesis in response to cold. In mice, most of the elevated rate of oxygen consumption of liver and skeletal muscle elicited by cold exposure is ouabain-sensitive. Thus, the Na+ pump appears to be an important heat source in the transition to homeothermy. The underlying biochemical mechanisms that mediate the contribution of the Na+ pump to heat production, including responsiveness to thyroid hormone and catecholamines, however, may not be unique to the homeotherms.

从变温到恒温的进化转变需要招募复杂的机制，这些机制在环境温度大幅变化的情况下既能提供更高的产热速率，又能调节热量散失。被认为有助于向恒温转变的两条途径是甲状腺调节的产热作用以及在适应寒冷过程中的非颤抖性产热。这些途径可能通过两个不一定相互排斥的过程在恒温动物中产生更高的产热速率：a）ATP水解以及随之产生Pi受体——ADP，或者b）线粒体氧化磷酸化的偶联减少。甲状腺和儿茶酚胺产热的很大一部分归因于主动跨膜Na⁺转运（即Na⁺泵）中能量消耗的增加。由此推断，这些发现表明Na⁺泵是恒温动物进化过程中的一个热源。甲状腺激素引起的产热反应在恒温动物（哺乳动物）中既迅速又显著，而在变温动物（两栖动物和爬行动物）中则更缓慢且明显程度可能较小。向恒温进化的一个关键途径可能是对寒冷作出反应的非颤抖性产热。在小鼠中，冷暴露引起的肝脏和骨骼肌耗氧率升高大部分对哇巴因敏感。因此，Na⁺泵似乎是向恒温转变过程中的一个重要热源。然而，介导Na⁺泵对产热作用的潜在生化机制，包括对甲状腺激素和儿茶酚胺的反应性，可能并非恒温动物所特有。