Fregly M J
Department of Physiology, University of Florida, College of Medicine, Gainesville 32610.
Pharmacol Ther. 1989;41(1-2):85-142. doi: 10.1016/0163-7258(89)90103-4.
It seems clear from the studies reviewed here that there is adequate evidence to support the concept of a biphasic response of the thyroid gland to cold as first postulated by Moll et al. (1972). The initial response to acute exposure to cold begins at the level of the hypothalamus as a result of either neural stimuli from skin and other areas and/or blood of somewhat lower than normal temperature reaching the hypothalamus (Andersson et al., 1963). As a result, the secretion of norepinephrine and/or dopamine may increase, and serotonin and/or somatostatin may decrease. The net result of these is an increase in the release of TRH from the hypothalamus. This, in turn, stimulates the cascade for the release of TSH from the anterior pituitary gland and thyroid hormone from the thyroid gland. Moll et al. (1972) postulated the lack of a feedback limb in this acute phase, and, indeed, this may be the case. It is possible, however, that certain hormones, such as somatostatin, norepinephrine, T3, and T4 could act in the capacity of feedback inhibitors. Additional experiments will be required to assess this possibility. The transitional link between the acute (less than 1 day) and chronic (greater than 1 day) phases of the response of the thyroid gland to cold could be T4 itself. An increase in the concentration of T4 in plasma has been reported to increase peripheral deiodination of T4 to T3 by kidneys and liver of rats. There are no studies at present to indicate that hepatic conjugation can be increased by elevation of plasma levels of T4 and T3. If it can, these responses would provide adequate reasons as to why peripheral metabolism of thyroid hormones increases during chronic exposure to cold. The time-course for these changes to occur needs to be studied in greater detail to establish the sequence of events following acute exposure to cold. The latter may also increase urinary excretion of T4 and T3 in man, but not the rat. This suggests that another aspect of exposure to cold needing additional study is measurement of the binding affinities of T4 and T3 for their transport proteins during exposure to cold as compared to affinities prior to exposure to cold. If binding affinities are reduced, the amount of free hormones would increase and, consequently the likelihood of being excreted into urine and conjugated by the liver would also increase.(ABSTRACT TRUNCATED AT 400 WORDS)
从这里回顾的研究来看，似乎有充分的证据支持莫尔等人（1972年）首次提出的甲状腺对寒冷产生双相反应的概念。对急性寒冷暴露的初始反应始于下丘脑水平，这是由于来自皮肤和其他区域的神经刺激和/或体温略低于正常的血液到达下丘脑所致（安德森等人，1963年）。结果，去甲肾上腺素和/或多巴胺的分泌可能增加，而血清素和/或生长抑素可能减少。这些变化的最终结果是下丘脑释放促甲状腺激素释放激素（TRH）增加。这反过来又刺激了垂体前叶释放促甲状腺激素（TSH）以及甲状腺释放甲状腺激素的级联反应。莫尔等人（1972年）推测在这个急性期缺乏反馈环节，实际上可能确实如此。然而，某些激素，如生长抑素、去甲肾上腺素、三碘甲状腺原氨酸（T3）和甲状腺素（T4）有可能作为反馈抑制剂起作用。需要进行更多实验来评估这种可能性。甲状腺对寒冷反应的急性（少于1天）和慢性（多于1天）阶段之间的过渡环节可能是T4本身。据报道，大鼠血浆中T4浓度的增加会使肾脏和肝脏将T4外周脱碘转化为T3增加。目前尚无研究表明血浆中T4和T3水平升高会增加肝脏结合作用。如果可以，这些反应将充分解释为什么在长期寒冷暴露期间甲状腺激素的外周代谢会增加。需要更详细地研究这些变化发生的时间进程，以确定急性寒冷暴露后事件的顺序。寒冷暴露还可能增加人体（而非大鼠）尿液中T4和T3的排泄。这表明寒冷暴露另一个需要进一步研究的方面是，与寒冷暴露前相比，测量寒冷暴露期间T4和T3与其转运蛋白的结合亲和力。如果结合亲和力降低，游离激素的量将增加，因此排泄到尿液中并被肝脏结合的可能性也会增加。（摘要截选至400字）
