Salvatore D, Tu H, Harney J W, Larsen P R
Thyroid Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
J Clin Invest. 1996 Aug 15;98(4):962-8. doi: 10.1172/JCI118880.
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 Km 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.
2型碘甲状腺原氨酸脱碘酶（D2）是最近克隆出的一种含硒脱碘酶，被认为能为一组特定组织提供细胞内的3,5,3'-三碘甲状腺原氨酸（T3）。我们在此报告，人类甲状腺中D2 mRNA的水平比胎盘高50 - 150倍。令人惊讶的是，虽然已知1型脱碘酶（D1）存在于人类甲状腺中，但此前尚未对D2进行评估。D2 mRNA在格雷夫斯病患者的甲状腺以及滤泡性腺瘤中尤其高。受刺激的甲状腺中D2与D1 mRNA的比率高于正常或多结节性腺体，这表明D1和D2的表达存在差异调节。来自正常、格雷夫斯病患者以及促甲状腺激素刺激的甲状腺的微粒体含有低Km的D2活性，对丙硫氧嘧啶（1 mM）或N - 溴乙酰T3失活具有抗性，而丙硫氧嘧啶和N - 溴乙酰T3是能阻断或使D1失活的试剂。在2 nM甲状腺素（T4）（是生理游离T4水平的100倍）时，受刺激的甲状腺中60 - 80%的T4向T3的转化由D2催化，但正常甲状腺中这一比例仅为27%。我们得出结论，D2介导的甲状腺内T4向T3的转化可能在格雷夫斯病、毒性腺瘤以及或许碘缺乏患者的甲状腺T3产生相对增加中起重要作用。
