AN ANALYSIS OF THE SOURCES AND QUANTITY OF 3,5,3'-TRIIODOTHYRONINE SPECIFICALLY BOUND TO NUCLEAR RECEPTORS IN RAT CEREBRAL-CORTEX AND CEREBELLUM
AN ANALYSIS OF THE SOURCES AND QUANTITY OF 3,5,3'-TRIIODOTHYRONINE SPECIFICALLY BOUND TO NUCLEAR RECEPTORS IN RAT CEREBRAL-CORTEX AND CEREBELLUM
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DOI：
10.1210/endo-110-2-367
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发表时间：
1982-01-01
期刊：
影响因子：
4.8
通讯作者：
LARSEN, PR
中科院分区：
文献类型：
--
作者：
CRANTZ, FR;SILVA, JE;LARSEN, PR
L-[125I]T4[甲状腺素]在大鼠大脑皮层和小脑内迅速转化为L- t3[三碘甲状腺原氨酸]。早期研究表明，大量的[125I]T3特异性结合核甲状腺激素受体。与同时注射[131I]T3相比，大脑皮层和小脑的细胞核中[125I]T3的含量高于其他组织，表明这些器官中局部产生的T3对核中总T3的贡献很大。评估了稳定状态下正常甲状腺大鼠大脑皮质和小脑核受体特异性结合的T3的相对贡献，即血浆和局部5”-去碘。为了确定这两种组织中核受体的最大结合能力，在标记T3的同时增加未标记T3的注射量。脑皮质核受体的最大结合能力为266 pg T3/mg DNA(95%置信限，242 ~ 290)，小脑核受体的最大结合能力为95 pg T3/mg DNA（89 ~ 101）。然后给予甲状腺功能正常的大鼠[125I]T4和[131I]T3，在适当修正血浆[125I]T3对核[125I]T3的贡献后，给予局部生成的核[125I]T3。计算局部（Lc） T3（T4）。注射[125I]T4后15h或更长时间，Lc T3（T4）占大脑皮质和apprx核[125I]T3总量的约80%。67%在小脑核中。注射后15 ~ 24 h，核Lc [125I]T3（T4）与血清[125I]T4比值保持不变。因此，核Lc T3（T4）的重量量通过将该比率乘以血清T4放射免疫测定来估计。此外，利用核[131I]T3峰值时的核与血清T3比值，以及血清T3放射免疫分析法来估计血浆T3对核T3的贡献。在大脑皮层中，核Lc T3（T4）为195 pg/mg DNA，占这些受体最大结合能力的73%。血浆T3贡献56 pg T3/mg DNA， 21%的结合能力，导致超过90%的核甲状腺激素受体占用。对于小脑，Lc T3（T4）为30 pg/mg DNA（最大结合容量的32%）；血浆T3贡献。23 pg/mg DNA或最大结合能力的24%。小脑核甲状腺激素受体占56%。细胞内由T4生成的T3占特异性结合到大脑皮层和小脑核受体的T3的一半以上。在内源性血清T3和T4浓度下，大脑皮层中的这些受体接近饱和。在中枢神经系统中，T4作为细胞内T3的来源显然起着重要作用。
There is rapid in vivo conversion of L-[125I]T4 [thyroxine] to L-T3 [triiodothyronine] in rat cerebral cortex and cerebellum. Early studies showed significant quantities of [125I]T3 specifically bound to nuclear thyroid hormone receptors. The amount of [125I]T3 relative to the simultaneously injected [131I]T3 in cell nuclei was greater in the cerebral cortex and cerebellum than in other tissues examined, suggesting a major contribution of locally generated T3 to total nuclear T3 in these organs. The relative contribution of both T3 sources, the plasma and local 5''-deiodination to the total mass of T3 specifically bound to the nuclear receptors of cerebral cortex and cerebellum in euthyroid rats in steady state conditions was assessed. To determine the maximal binding capacity of the nuclear receptors in these 2 tissues, rats were injected with increasing quantities of unlabeled T3 along with labeled T3. The maximal binding capacity of the nuclear receptors in cerebral cortex was 266 pg T3/mg DNA (95% confidence limits, 242-290) and that for cerebellum was 95 pg T3/mg DNA (89-101). Euthyroid rats were then given [125I]T4 and [131I]T3 and after suitable corrections for the contribution of plasma [125I]T3 to nuclear [125I]T3, they were given the locally generated nuclear [125I]T3. Local (Lc) T3(T4), was computed. At 15 h or longer after [125I]T4 injection, Lc T3(T4) accounted for > 80% of the total nuclear [125I]T3 in cerebral cortex and .apprx. 67% of that in the cerebellar nuclei. The nuclear Lc [125I]T3(T4) to serum [125I]T4 ratio was constant between 15 and 24 h after the injection. The gravimetric amount of nuclear Lc T3(T4) was thus estimated by multiplying this ratio by serum T4 radioimmunoassay. In addition, the nuclear to serum ratio for T3, at the peak of nuclear [131I]T3, and the serum T3 radioimmunoassay were used to estimate the contribution of plasma T3 to nuclear T3. In the cerebral cortex, nuclear Lc T3(T4) was 195 pg/mg DNA occupying 73% of the maximal binding capacity of these receptors. Plasma T3 contributed 56 pg T3/mg DNA, 21% of the binding capacity, resulting in over 90% occupancy of the nuclear thyroid hormone receptors. For cerebellum, Lc T3(T4) was 30 pg/mg DNA (32% of the maximal binding capacity); plasma T3 contributed .apprx. 23 pg/mg DNA or 24% of the maximal binding capacity. The occupancy of cerebellar nuclear thyroid hormone receptors was 56%. T3 generated intracellularly from T4 contributes more than half of the T3 specifically bound to nuclear receptors of cerebral cortex and cerebellum. These receptors in cerebral cortex are nearly saturated at endogenous serum T3 and T4 concentrations. T4 apparently plays an important role as a source of intracellular T3 in the CNS.