van Doorn J, Roelfsema F, van der Heide D
Endocrinology. 1985 Sep;117(3):1201-8. doi: 10.1210/endo-117-3-1201.
The present study was designed to assess the quantities of T4 and T3, and the source (i.e. plasma-derived vs. locally produced) of the latter iodothyronine, in various rat tissues. For this purpose, normal intact rats were brought to isotopic equilibrium by means of a continuous iv infusion of [125I]T4 and [131I]T3 for a prolonged period. At the end of the infusion period, the animals were bled and perfused. Either whole small organs or weighed portions of tissues were homogenized in saline. The iodothyronines were extracted with ethanol-ammonia and separated by TLC. The [125I]T3/[131I]T3 ratios for the tissue homogenates and plasma were determined, and the relative contribution of the T3 derived from local T4 to T3 conversion [abbreviated: Lc T3 (T4)] to the total T3 in a given tissue was calculated. The endogenous T4 and T3 levels in the various organs were computed from the known specific activities of the labeled iodothyronines. The concentration of T4 in plasma greatly exceeded that found for tissue. Among the tissues examined, the T4 concentration was highest in the liver and lowest in cerebral cortex and cerebellum. T3 (per gram) was most abundant in the kidney and anterior pituitary gland and least abundant in the testis, epididymis, and erythrocytes. In contrast to the other tissues investigated, the concentration of T3 in several regions of the brain and anterior pituitary gland either equalled or exceeded that of T4. Plasma exhibited by far the lowest T3/T4 ratio. For most of the organs investigated the contribution of Lc T3(T4) appeared to be low. On the other hand, in 15 tissues, including the central nervous system, the local production of T3 accounted for one fifth or more of the total T3 content. Although there were no regional differences between the total T3 levels in the brain, the relative contribution of Lc T3(T4) was 65% in the cerebral cortex and only 22% in the spinal cord. The variation in the source of T3 in the various parts of the central nervous system may be related to regional differences in T4 and T3 metabolism. The fact that the present study demonstrates that the relationship between circulating T3 and intracellular T3 varies from one organ to the next may be important for accurate interpretation of plasma T4 and T3 levels and for designing optimal thyroid hormone replacement therapy for patients with hypothyroidism.
本研究旨在评估各种大鼠组织中T4和T3的含量,以及后一种碘甲状腺原氨酸的来源(即血浆来源与局部产生)。为此,通过长时间持续静脉输注[125I]T4和[131I]T3,使正常完整大鼠达到同位素平衡。在输注期结束时,对动物进行采血和灌注。将整个小器官或称重的组织部分在盐水中匀浆。用乙醇-氨水提取碘甲状腺原氨酸,并用薄层层析法进行分离。测定组织匀浆和血浆的[125I]T3/[131I]T3比值,并计算局部T4转化为T3 [缩写:Lc T3 (T4)] 对给定组织中总T3的相对贡献。根据标记碘甲状腺原氨酸的已知比活性计算各器官中的内源性T4和T3水平。血浆中T4的浓度大大超过组织中的浓度。在所检查的组织中,肝脏中的T4浓度最高,大脑皮层和小脑中的浓度最低。T3(每克)在肾脏和垂体前叶中含量最丰富,在睾丸、附睾和红细胞中含量最少。与其他研究的组织相比,大脑和垂体前叶几个区域的T3浓度等于或超过T4浓度。血浆的T3/T4比值是迄今为止最低的。对于大多数研究的器官,Lc T3(T4)的贡献似乎较低。另一方面,在包括中枢神经系统在内的15种组织中,T3的局部产生占总T3含量的五分之一或更多。虽然大脑中总T3水平没有区域差异,但Lc T3(T4)在大脑皮层中的相对贡献为65%,在脊髓中仅为22%。中枢神经系统各部位T3来源的差异可能与T4和T3代谢的区域差异有关。本研究表明循环T3与细胞内T3之间的关系因器官而异,这一事实对于准确解释血浆T4和T3水平以及为甲状腺功能减退患者设计最佳甲状腺激素替代疗法可能很重要。