High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase
High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase
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Mct8 缺乏症患者的高 T3、低 T4 血清水平并不是由 I 型脱碘酶促进肝脏转化增加引起的
DOI：
10.1159/000381021
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发表时间：
--
影响因子：
4.7
通讯作者：
Schweizer U
中科院分区：
文献类型：
--
作者：
Wirth EK;Rijntjes E;Meyer F;Köhrle J;Schweizer U
背景：Allan-Herndon-Dudley综合征是一种严重的精神运动发育迟缓，伴有循环甲状腺激素水平的特殊变化(高T3，低T4)。这些疾病是由甲状腺激素跨膜转运蛋白单羧酸转运蛋白8(MCT8)突变引起的。目的：验证循环中低T4和高T3水平是由于肝脏I型脱碘酶(Dio1)活性升高而T4转化增强所致的假说。方法：将Mct8基因缺陷小鼠与肝细胞Dio1活性缺失小鼠杂交。硒酶Dio1的翻译被肝细胞特异性的硒蛋白生物合成失活所废除。结果：整体Mct8缺陷小鼠肝脏中Dio1活性的失活并不能恢复正常的循环甲状腺激素水平。结论：我们的数据表明，尽管Mct8缺陷小鼠的肝脏Dio1活性增加，但它不会导致观察到的循环甲状腺激素水平异常。由于Mct8基因缺陷小鼠体内Dio1的整体失活确实能使循环中的甲状腺激素水平恢复正常，其潜在的机制和涉及的相关组织尚不清楚。背景：Allan-Herndon-Dudley综合征是一种严重的精神运动发育迟缓，伴有循环甲状腺激素水平的特殊变化(高T3，低T4)。这些疾病是由甲状腺激素跨膜转运蛋白单羧酸转运蛋白8(MCT8)突变引起的。目的：验证循环中低T4和高T3水平是由于肝脏I型脱碘酶(Dio1)活性升高而T4转化增强所致的假说。方法：将Mct8基因缺陷小鼠与肝细胞Dio1活性缺失小鼠杂交。硒酶Dio1的翻译被肝细胞特异性的硒蛋白生物合成失活所废除。结果：整体Mct8缺陷小鼠肝脏中Dio1活性的失活并不能恢复正常的循环甲状腺激素水平。结论：我们的数据表明，尽管Mct8缺陷小鼠的肝脏Dio1活性增加，但它不会导致观察到的循环甲状腺激素水平异常。由于Mct8基因缺陷小鼠体内Dio1的整体失活确实能使循环中的甲状腺激素水平恢复正常，其潜在的机制和涉及的相关组织仍有待阐明。
Background: The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4and high T3levels are caused by enhanced conversion of T4via increased activity of hepatic type I deiodinase (Dio1). Methods: We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results: Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions: Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.AbstractBackground: The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4and high T3levels are caused by enhanced conversion of T4via increased activity of hepatic type I deiodinase (Dio1). Methods: We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results: Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions: Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.
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单羧酸转运蛋白 8 缺乏对小鼠下丘脑-垂体-甲状腺轴的影响。
影响因子：
4.8
作者：
M. Trajkovic;Julia Müller;V. Darras;Claudia Groba;Sooyeon Lee;Debra S. Weih;K. Bauer;T. Visser;H. Heuer
通讯作者：
H. Heuer
肝脱碘酶活性对于维持小鼠正常循环甲状腺激素水平是可有可无的。
DOI：
--
发表时间：
2005
期刊：
Biochemical and Biophysical Research Communications - BBRC
影响因子：
--
作者：
F. Streckfuss;I. Hamann;L. Schomburg;M. Michaelis;R. Sapin;M. Klein;J. Köhrle;U. Schweizer
通讯作者：
U. Schweizer
影响因子：
4.1
作者：
Schweizer, U;Streckfuss, F;Schomburg, L
通讯作者：
Schomburg, L
单羧酸转运蛋白 8 缺乏：甲状腺形态改变，甲状腺切除术后三碘甲状腺原氨酸/甲状腺素比率持续升高。
影响因子：
5.8
作者：
E. Wirth;S. Sheu;J. Chiu;R. Sapin;M. Klein;I. Mossbrugger;L. Quintanilla‐Martinez;M. D. de Angelis;H. Krude;T. Riebel;K. Rothe;J. Köhrle;K. Schmid;U. Schweizer;A. Grüters
通讯作者：
A. Grüters
影响因子：
168.9
作者：
Friesema, ECH;Grueters, A;Visser, T
通讯作者：
Visser, T