van Doorn J, Roelfsema F, van der Heide D
Acta Endocrinol (Copenh). 1983 Aug;103(4):509-20. doi: 10.1530/acta.0.1030509.
The effect of prolonged oral administration of PTU and MMI on the local conversion of T4 to T3 was studied in T4-maintained athyreotic rats. For this purpose the rats were equilibrated with [125I]T4 and [131I]T3 by means of continuous iv infusions. PTU treatment reduced the MCR of both T4 and T3, as well as the T3 levels in plasma, muscle, liver, kidney and cerebellum. In the cerebral cortex the total intracellular T3 concentration was not affected, while in the pituitary it even increased. The amount of T3 derived from local conversion of T4 to T3 (LcT3(T4)) was reduced in the liver. PTU treatment did not influence Lc T3(T4) in the cerebellum, but did cause an increase in the amount of T3 derived from this source in the cerebral cortex and the pituitary gland (both the homogenate and the nuclear fraction). The results indicate that in contrast to that in liver, local T3 production in the brain and pituitary must occur predominantly via a pathway which is not inhibited by PTU. In MMI-treated rats the total T3 concentration in the cerebral cortex and cerebellum was not altered, whereas both the MCR of T3 and the T3 levels in plasma and various other tissues were elevated. The relative contribution of Lc T3(T4) increased in liver and was reduced in the cerebral cortex, cerebellum and pituitary gland. In all experiments in liver the contribution of Lc T3(T4) to nuclear T3 was negligible, whereas this was not the case for the other hepatic subcellular fractions. As in liver, virtually all renal nuclear T3 was derived from plasma. The present findings suggest that the production of T3 in liver and kidney, and its subsequent release into the blood, may provide a mechanism for the regulation of plasma T3 levels but is not a direct source of their nuclear T3. In the pituitary gland and the brain local T4 to T3 conversion functions as a source of T3 for the control of local utilization. In this respect the maintainance of constant T3 levels in the brain might be important. These differences among tissues suggest that different mechanisms are involved in T4 5'-deiodination.
在以T4维持的甲状腺切除大鼠中，研究了长期口服丙硫氧嘧啶（PTU）和甲巯咪唑（MMI）对T4在局部转化为T3的影响。为此，通过连续静脉输注使大鼠用[125I]T4和[131I]T3达到平衡。PTU治疗降低了T4和T3的代谢清除率（MCR），以及血浆、肌肉、肝脏、肾脏和小脑中的T3水平。在大脑皮层，细胞内总T3浓度未受影响，而在垂体中甚至升高。肝脏中由T4局部转化为T3（LcT3(T4)）产生的T3量减少。PTU治疗不影响小脑中的Lc T3(T4)，但确实导致大脑皮层和垂体（匀浆和核部分）中源自该来源的T3量增加。结果表明，与肝脏不同，大脑和垂体中的局部T3产生主要通过一条不受PTU抑制的途径进行。在MMI治疗的大鼠中，大脑皮层和小脑中的总T3浓度未改变，而T3的MCR以及血浆和其他各种组织中的T3水平均升高。Lc T3(T4)的相对贡献在肝脏中增加，而在大脑皮层、小脑和垂体中减少。在肝脏的所有实验中，Lc T3(T4)对核T3的贡献可忽略不计，而其他肝亚细胞部分则并非如此。与肝脏一样，几乎所有肾核T3均源自血浆。目前的研究结果表明，肝脏和肾脏中T3的产生及其随后释放到血液中，可能提供了一种调节血浆T3水平的机制，但不是其核T3的直接来源。在垂体和大脑中，局部T4向T3的转化作为控制局部利用的T3来源。在这方面，维持大脑中恒定的T3水平可能很重要。组织间的这些差异表明，T4 5'-脱碘涉及不同的机制。
