The type 2 and type 3 iodothyronine deiodinases play important roles in coordinating development in Rana catesbeiana tadpoles
The type 2 and type 3 iodothyronine deiodinases play important roles in coordinating development in Rana catesbeiana tadpoles
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DOI：
10.1210/en.138.7.2989
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发表时间：
1997-07-01
期刊：
影响因子：
4.8
通讯作者：
Galton, VA
中科院分区：
文献类型：
--
作者：
Becker, KB;Stephens, KC;Galton, VA
在发育中的林蛙蝌蚪中，甲状腺激素（TH）依赖性变态反应的时间在组织之间存在显着差异。然而，在任何时候，这些组织都暴露于相同的 TH 血浆浓度，这表明 TH 作用部分在外周组织水平上受到调节。 TH 作用的一个主要因素是细胞内活性 TH（T-3）的水平。该水平不仅取决于 TH（主要是 T-4）的血浆浓度，还取决于 25'-脱碘酶（D2）型和 35-脱碘酶（D3）型的细胞内活性，它们分别负责生成和降解 T-3。 （该物种中不存在 D1。）为了确定组织中 D2 和 D3 的差异表达是否可能是协调变态事件的重要因素，两种酶活性的个体发育谱和 R.catesbeiana 蝌蚪大多数组织中相应的信使 RNA 水平已被记录。 D2 在尾部、后肢、前肢、肠道、皮肤和眼睛中的表达谱在活性和信使 RNA 水平上都有显着差异，但值得注意的是，在给定组织发生主要变质变化时，表达总是最高的。 D2 的表达在大脑和心脏中非常低，并且在发育过程中没有变化。 D2 在肝、肾或红细胞中不表达。除红细胞外，在所有研究的组织中均检测到 D3 表达。此外，很明显，在表达两种脱碘酶基因的组织中，两种表达谱具有可比性，表明细胞内 T-3 水平有严格控制的潜力。在蝌蚪中获得了细胞内 T-4 转化为 T-3 对于 TH 依赖性变态事件重要性的直接证据，其中内源性 TH 合成被他巴唑阻断，D2 和 D3 的活性被碘番酸抑制。这种治疗抑制了变态。这种抑制可以通过同时施用替代水平的 T-3 而不是 T-4 来克服。这些结果强烈支持这样的观点，即两栖动物的协调发育部分取决于 D2 和 D3 基因的组织特异性表达模式，这确保了在变态的适当阶段，无论循环 TK 的当前水平如何，在给定组织中达到所需的细胞内 T-3 水平。
In developing Rana catesbeiana tadpoles, the timing of the thyroid hormone (TH)-dependent metamorphic responses varies markedly among tissues. Yet at any one time these tissues are exposed to the same plasma concentration of TH, suggesting that TH action is regulated in part at the level of the peripheral tissues. A major factor in TH action is the intracellular level of the active TH, T-3. This level is dependent not only on the plasma concentration of TH (mostly T-4) but also on the intracellular activities of the type 25'-deiodinase (D2) and the type 35-deiodinase (D3), which are responsible, respectively, for generating and degrading T-3. (D1 is not present in this species.) To determine whether differential expression of D2 and D3 among tissues could be a significant factor in the coordination of metamorphic events, the ontogenic profiles of the two enzyme activities and corresponding messenger RNA levels in most tissues of R. catesbeiana tadpoles have been documented. The profiles of D2 expression in tail, hindlimb, forelimb, intestine, skin, and eye differed markedly at both activity and messenger RNA levels, but it was notable that expression was invariably highest in a given tissue at the time of its major metamorphic change. D2 expression was very low in brain and heart and did not Vary during development. D2 was not expressed in liver, kidney, or red blood cells. With the exception of red blood cells, D3 expression was detected in all tissues studied. Furthermore, it was evident that in tissues that expressed both deiodinase genes, the two expression profiles were comparable, indicating a potential for tight control of intracellular T-3 levels.Direct evidence of the importance of the intracellular conversion of T-4 to T-3 for TH-dependent metamorphic events was obtained in tadpoles in which endogenous TH synthesis was blocked with methimazole, and the activities of D2 and D3 were inhibited by iopanoic acid. This treatment inhibited metamorphosis. The inhibition could be overcome by the concomitant administration of replacement levels of T-3, but not T-4.These results strongly support the view that coordinated development in amphibia depends in part on the tissue-specific expression patterns of the D2 and D3 genes, which ensure that the requisite level of intracellular T-3 is attained in a given tissue, regardless of the current level of circulating TK, at the appropriate stage of metamorphosis.