Quantitation of extrathyroidal conversion of L-thyroxine to 3,5,3'-triiodo-L-thyronine in the rat.

Quantitation of extrathyroidal conversion of L-thyroxine to 3,5,3'-triiodo-L-thyronine in the rat.
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大鼠体内 L-甲状腺素甲状腺外转化为 3,5,3-三碘-L-甲状腺氨酸的定量。

DOI:
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发表时间:
1971
影响因子:
15.9
通讯作者:
J. Oppenheimer
J. Oppenheimer
中科院分区:
医学1区
文献类型:
--
作者:
H. L. Schwartz;M. Surks;J. Oppenheimer

文献摘要

被引文献

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本文研究了大鼠甲状腺外甲状腺素(T_4)转化为3,5,3 ′-三碘-L-甲状腺原氨酸(T_3)的速率。在静脉注射(125)I-T4后48、72和96 h,制备全身匀浆,并用乙醇提取。加入(131)I-T3,通过连续洗脱和再色谱法在三个纸和一个薄层循环中进行T3的纸色谱纯化。最终色谱图中(131)I-T3和(125)I-T3计数率的比值(在三种不同纸色谱系统中相同)用于计算原始匀浆中(125)I-T3与(125)I-T4的比例。为了消除提取和层析过程中T4体外单脱碘的影响,我们在注射(125)I-T4后立即处死对照动物,并以与实验组相似的方式处理它们。在同位素注射后48至96小时之间处死的动物尸体提取物中(125)I-T3与(125)I-T4的平均比值为0.08,而对照动物色谱图中(125)I-T3与(125)I-T4的平均比值为0.01。在所提出的模型的基础上,计算表明,约17%的分泌的T4转化为T3。假设文献中引用的大鼠血浆中非放射性T3浓度值,这些结果表明,约20%的全身T3是由T4转化而来的。此外,由于先前的估计表明,在大鼠中,T3的生物活性比T4高约3至5倍,这些结果也提出了T4的激素活性可能在很大程度上取决于它向T3的转化的可能性,在本研究和其他研究中计算T4向T3转化的一个必要的假设是,3'和5'位置被放射性碘随机标记酚环碘标记的T4。通过比较大鼠注射酚环和非酚环碘标记T4后产生的标记T3的量,获得了支持这一假设的证据。
Studies of the rate of extrathyroidal conversion of thyroxine (T4) to 3,5,3'-triiodo-L-thyronine (T3) were carried out in rats. Total body homogenates were prepared and extracted with ethanol 48, 72, and 96 hr after the intravenous injection of (125)I-T4. (131)I-T3 was added, and the paper chromatographic purification of T3 was effected by serial elution and rechromatography in three paper and one thin-layer cycles. The ratio of (131)I-T3 and (125)I-T3 counting rates in the final chromatograms, which was identical in three different paper chromatography systems, was used to calculate the proportion of (125)I-T3 to (125)I-T4 in the original homogenates. In order to discount the effects of in vitro monodeiodination of T4 during extraction and chromatography, we killed control animals immediately after injection of (125)I-T4 and processed them in a similar fashion to the experimental groups. The average ratio of (125)I-T3 to (125)I-T4 in carcass extracts of animals killed between 48 and 96 hr after isotopic injection was 0.08 whereas the average ratio of (125)I-T3 to (125)I-T4 in chromatograms of control animals was 0.01. On the basis of the proposed model, calculations indicated that about 17% of the secreted T4 was converted to T3. Assuming values cited in the literature for the concentration of nonradioactive T3 in rat plasma, these findings would suggest that about 20% of total body T3 is derived by conversion from T4. Moreover, since previous estimates have suggested that in the rat, T3 has about 3 to 5 times greater biologic activity than T4, these results also raise the possibility that the hormonal activity of T4 may be dependent in large part on its conversion to T3.A necessary assumption in calculating T4 to T3 conversion in this and other studies is that the 3' and 5' positions are randomly labeled with radioiodine in phenolic-ring iodine-labeled T4. Evidence supporting this assumption was obtained in the rat by comparing the amount of labeled T3 produced after injection of phenolic and nonphenolic-ring iodine-labeled T4.