Maeda M, Ingbar S H
Endocrinology. 1984 Mar;114(3):747-52. doi: 10.1210/endo-114-3-747.
Studies were directed at the question of whether the enzyme that mediates the 5'- or outer ring monodeiodination of T4 is the same as that which mediates the 5'-monodeiodination of rT3. Advantage was taken of previous observations which indicated that T3, when administered to the hypothyroid rat, acutely inhibits the 5'-monodeiodination of T4 to yield T3 in hemipituitaries in vitro. In the present experiments, these effects of T3 on the generation of T3 from T4 were confirmed in both hemipituitaries and homogenates, indicating that they were not due to an effect of T3 on the cellular penetration of the [125I]T4 used as substrate. In contrast, in separate experiments with both hemipituitaries and homogenates, T3 had no effect on the metabolism of [125I]rT3, including its 5'-monodeiodination to yield 3,3'-diiodothyronine. In other experiments, the divergent effects of T3 on the metabolism of T4 and rT3 were also observed when the two substrates were studied in paired hemipituitaries and paired aliquots of the same pituitary homogenate. Failure of T3 to inhibit the 5'-monodeiodination of rT3 in pituitary homogenates could not be explained by the presence of marked enzyme excess, since T3 was also without effect when homogenates were incubated with rT3 at a concentration of 1 microgram/ml. In additional experiments, propylthiouracil (PTU) in vitro (1 mM) was found to have no effects on either the rapid metabolism of [125I]T4 seen in the pituitaries of hypothyroid rats or the less rapid metabolism of [125I]T4 seen in pituitaries of hypothyroid rats given T3. In contrast, though PTU failed to alter the metabolism of [125I]rT3 in pituitaries of hypothyroid rats, it greatly inhibited the metabolism of [125I]rT3 in the pituitaries of hypothyroid rats given T3. These results are consistent with those in previous reports which indicate that the pituitary contains two enzymes that mediate the deiodination of T4 and rT3. One is a PTU-insensitive enzyme that mediates the 5'-monodeiodination of T4; its activity is increased in hypothyroidism and is decreased by T3 replacement. The other is a PTU-sensitive enzyme that mediates much of the 5'-monodeiodination of rT3 in the pituitary of the T3-replaced rat, as in the euthyroid rat, but whose activity is largely supplanted by that of the PTU-insensitive enzyme in hypothyroidism.
研究围绕介导T4的5'-或外环单碘化作用的酶是否与介导反T3的5'-单碘化作用的酶相同这一问题展开。利用了先前的观察结果，即给甲状腺功能减退的大鼠注射T3后，会急性抑制体外半垂体中T4的5'-单碘化作用以产生T3。在本实验中，T3对T4生成T3的这些作用在半垂体和匀浆中均得到证实，表明它们并非由于T3对用作底物的[125I]T4的细胞穿透作用产生的影响。相反，在分别对半垂体和匀浆进行的实验中，T3对[125I]反T3的代谢没有影响，包括其5'-单碘化作用生成3,3'-二碘甲腺原氨酸。在其他实验中，当在配对的半垂体和同一垂体匀浆的配对等分试样中研究这两种底物时，也观察到了T3对T4和反T3代谢的不同影响。T3未能抑制垂体匀浆中反T3的5'-单碘化作用，这不能用存在明显的酶过量来解释，因为当匀浆与浓度为1微克/毫升的反T3一起孵育时，T3也没有作用。在另外的实验中，发现体外丙硫氧嘧啶（PTU）（1毫摩尔）对甲状腺功能减退大鼠垂体中[125I]T4的快速代谢或给予T3的甲状腺功能减退大鼠垂体中[125I]T4较慢的代谢均无影响。相比之下，尽管PTU未能改变甲状腺功能减退大鼠垂体中[125I]反T3的代谢，但它极大地抑制了给予T3的甲状腺功能减退大鼠垂体中[125I]反T3的代谢。这些结果与先前报告中的结果一致，表明垂体含有两种介导T4和反T3脱碘作用的酶。一种是对PTU不敏感的酶，介导T4的5'-单碘化作用；其活性在甲状腺功能减退时增加，在给予T3替代治疗时降低。另一种是对PTU敏感的酶，在给予T3的大鼠垂体中，如同在甲状腺功能正常的大鼠中一样，介导反T3的大部分5'-单碘化作用，但其活性在甲状腺功能减退时在很大程度上被对PTU不敏感的酶的活性所取代。
