Towle H C, Dillmann W H, Schwartz H L, Oppenheimer J H
Prog Clin Biol Res. 1979;31:691-701.
Although the molecular basis of thyroid hormone action remains obscure, a growing body of evidence has suggested that triiodothyronine (T3) action is initiated at a set of specific nuclear receptor sites. The physiologic significance of these T3-binding sites is supported by four lines of evidence: 1) the high-affinity, limited-capacity binding of T3; 2) the relationship between binding affinity of thyroid hormone analogs and hormonal potency; 3) the correlation of concentration of nuclear receptor and physiologic response in various tissues; 4) the relationship between receptor occupancy and physiologic response. While the levels of hepatic nuclear receptor do not change in response to T3, recent evidence indicates receptor concentration is markedly reduced by partial hepatectomy, starvation, or administration of glucagon. This reduction results in a decrease in the response of malic enzyme to T3, but leaves the response of alpha-glycerol phosphate dehydrogenase unimpaired. Thus, specific control of thyroid responses by modulating receptor concentration may occur. Occupancy of hepatic receptors by T3 is associated with increases in both the rate of formation and steady-state concentration of poly(A)-containing mRNA. The values of these two parameters in the euthyroid rat liver were approximately 60--80% greater than values in hypothyroid animals. Analyses of the sequence and frequency complexity of poly(A)-containing mRNA from euthyroid and hypothyroid rats revealed no major changes in either the qualitative or quantitative distribution of mRNA sequences. Although it is recognized that the levels of certain specific species of mRNA (ie, alpha 2u-globulin) are altered as a result of thyroid hormone action, these data strongly indicate a concomitant generalized increase in the production of all major classes of mRNA.
尽管甲状腺激素作用的分子基础仍不清楚，但越来越多的证据表明，三碘甲状腺原氨酸（T3）的作用是在一组特定的核受体位点启动的。这些T3结合位点的生理意义得到了四条证据的支持：1）T3的高亲和力、有限容量结合；2）甲状腺激素类似物的结合亲和力与激素效力之间的关系；3）各种组织中核受体浓度与生理反应的相关性；4）受体占有率与生理反应之间的关系。虽然肝细胞核受体的水平不会因T3而改变，但最近的证据表明，部分肝切除、饥饿或给予胰高血糖素会使受体浓度显著降低。这种降低导致苹果酸酶对T3的反应下降，但α-甘油磷酸脱氢酶的反应不受影响。因此，可能通过调节受体浓度对甲状腺反应进行特异性控制。T3占据肝受体与含多聚腺苷酸（poly(A)）的mRNA的形成速率和稳态浓度的增加有关。正常甲状腺大鼠肝脏中这两个参数的值比甲状腺功能减退动物的值大约高60%-80%。对正常甲状腺和甲状腺功能减退大鼠含poly(A)的mRNA的序列和频率复杂性分析表明，mRNA序列的定性或定量分布均无重大变化。尽管人们认识到某些特定种类的mRNA（即α2u球蛋白）的水平会因甲状腺激素的作用而改变，但这些数据强烈表明，所有主要类别的mRNA的产生同时普遍增加。
