Cloning of the mammalian type II iodothyronine deiodinase - A selenoprotein differentially expressed and regulated in human and rat brain and other tissues
Cloning of the mammalian type II iodothyronine deiodinase - A selenoprotein differentially expressed and regulated in human and rat brain and other tissues
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DOI：
10.1172/jci118806
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发表时间：
1996-07-15
影响因子：
15.9
通讯作者：
StGermain, DL
中科院分区：
文献类型：
--
作者：
Croteau, W;Davey, JC;StGermain, DL
甲状腺外组织中甲状腺激素的脱碘在调节甲状腺激素的作用中起着重要作用。II型脱碘酶(DII)将甲状腺激素转化为活性激素3，5，3‘-三碘甲腺原氨酸，在大鼠的大脑、脑下垂体和棕色脂肪组织(BAT)中表达。I型和III型脱碘酶(分别为DI和DIII)的互补DNA(CDNA)已被分离出来，并被证明编码硒蛋白。然而，关于哺乳动物DII的结构的信息仍然有限，其在人体组织中的表达模式也不确定。在此，我们报告了大鼠和人DII基因的鉴定和特性。两者都编码硒蛋白，并与DI和DIII显示有限的同源性区域。在大鼠脑垂体和蝙蝠中，DII mRNA水平因动物甲状腺激素状态的变化而变化10倍以上。对来自人类组织的RNA进行Northern分析，发现DiI转录本在心脏、骨骼肌、胎盘、胎儿大脑和成人大脑的几个区域都有表达。这些研究表明：(A)大鼠和人DII是硒蛋白，(B)DII在大鼠中的表达至少部分地在某些组织的翻译前水平上被调节，以及(C)DII在人类胎儿和成人的甲状腺激素经济中可能具有相当大的生理重要性。
The deiodination of thyroid hormones in extrathyroidal tissues plays an important role in modulating thyroid hormone action. The type II deiodinase (DII) converts thyroxine to the active hormone 3,5,3'-triiodothyronine, and in the rat is expressed in the brain, pituitary gland, and brown adipose tissue (BAT). Complementary DNAs (cDNAs) for the types I and III deiodinases (DI and DIII, respectively) have been isolated and shown to code for selenoproteins. However, information concerning the structure of the mammalian DII remains limited, and the pattern of its expression in human tissues is undefined. we report herein the identification and characterization of rat and human DII cDNAs. Both code for selenoproteins and exhibit limited regions of homology with the DI and DIII. In the rat pituitary and BAT, DII mRNA levels are altered more than 10-fold by changes in the thyroid hormone status of the animal. Northern analysis of RNA derived from human tissues reveals expression of DII transcripts in heart, skeletal muscle, placenta, fetal brain, and several regions of the adult brain. These studies demonstrate that: (a) the rat and human DII are selenoproteins, (b) DII expression in the rat is regulated, at least in part, at the pretranslational level in some tissues, and (c) DII is likely to be of considerable physiologic importance in throid hormone economy in the human fetus and adult.