Type 2 iodothyronine deiodinase is highly expressed in human thyroid
Type 2 iodothyronine deiodinase is highly expressed in human thyroid
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DOI：
10.1172/jci118880
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发表时间：
1996-08-15
影响因子：
15.9
通讯作者：
Larsen, PR
中科院分区：
文献类型：
--
作者：
Salvatore, D;Tu, H;Larsen, PR
二碘甲腺原氨酸脱碘酶(D2)是新近克隆的一种硒脱碘酶，被认为是一种提供细胞内3，5，3‘三碘甲腺原氨酸(T3)的酶。我们在这里报道了人类甲状腺中D2mRNA的表达水平是胎盘的50-150倍，令人惊讶的是，虽然已知1型脱碘酶(D1)存在于人甲状腺中，但D2以前没有被评估过。D2mRNA在Graves病患者和滤泡性腺瘤中尤其高，受刺激的甲状腺具有比正常或多结节腺体更高的D2/D1mRNA比率，这表明D1和D2的表达存在差异调节。来自正常、Graves‘和TSH刺激的甲状腺微粒体含有低K-mD2活性，抵抗丙基硫氧嘧啶(1 MM)或N-溴乙酰T3失活，在2 nM甲状腺素(T4)，100倍的无生理水平的T4水平，60-80%的T4到T3的转化，但在正常甲状腺中只有27%的D2被D2催化。我们的结论是，D2在甲状腺内将T4转化为T3可能是Graves病、中毒性腺瘤以及可能缺碘患者甲状腺T3产量相对增加的重要原因。
Type 2 iodothyronine deiodinase (D2) is a recently cloned selenodeiodinase thought to provide intracellular 3,5,3' triiodothyronine (T3) to a restricted group of tissues, We report here the presence of D2 mRNA in human thyroid at levels 50-150-fold higher than in placenta, Surprisingly, while type 1 deiodinase (D1) is known to be present in human thyroid, D2 has not been evaluated previously. D2 mRNA was especially high in thyroids from Graves' patients and in follicular adenomas, Stimulated thyroids had higher D2 to D1 mRNA ratios than normal or multinodular glands suggesting differential regulation of D1 and D2 expression, Microsomes from normal, Graves', and TSH-stimulated thyroids contained low K-m D2 activity resistant to propylthiouracil (1 mM) or to inactivation by N-bromoacetyl T3, agents which block or inactivate D1, At 2 nM thyroxine (T4), 100 times the physiological-free T4 levels, 60-80% of T4 to T3 conversion in stimulated, but only 27% of that in normal thyroids, is catalyzed by D2, We conclude that intrathyroidal T4 to T3 conversion by D2 may contribute significantly to the relative increase in thyroidal T3 production in patients with Graves' disease, toxic adenomas, and, perhaps, iodine deficiency.