Department of Histology and Embryology, School of Basic Medical Sciences, Southwest Medical University, China.
Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China.
Endocrinol Metab (Seoul). 2023 Apr;38(2):190-202. doi: 10.3803/EnM.2022.1599. Epub 2023 Apr 27.
Type II deiodinase (DIO2) is thought to provide triiodothyronine (T3) to the nucleus to meet intracellular needs by deiodinating the prohormone thyroxine. DIO2 is expressed widely in many tissues and plays an important role in a variety of physiological processes, such as controlling T3 content in developing tissues (e.g., bone, muscles, and skin) and the adult brain, and regulating adaptive thermogenesis in brown adipose tissue (BAT). However, the identification and cloning of DIO2 have been challenging. In recent years, several clinical investigations have focused on the Thr92Ala polymorphism, which is closely correlated with clinical syndromes such as type 2 diabetes, obesity, hypertension, and osteoarthritis. Thr92Ala-DIO2 was also found to be related to bone and neurodegenerative diseases and tumors. However, relatively few reviews have synthesized research on individual deiodinases, especially DIO2, in the past 5 years. This review summarizes current knowledge regarding the physiological functions of DIO2 in thyroid hormone signaling and adaptive thermogenesis in BAT and the brain, as well as the associations between Thr92Ala-DIO2 and bone and neurodegenerative diseases and tumors. This discussion is expected to provide insights into the physiological functions of DIO2 and the clinical syndromes associated with Thr92Ala-DIO2.
II 型脱碘酶（DIO2）被认为通过将前激素甲状腺素脱碘来为细胞核提供三碘甲状腺原氨酸（T3）以满足细胞内的需求。DIO2 在许多组织中广泛表达，在各种生理过程中发挥着重要作用，例如控制发育组织（如骨骼、肌肉和皮肤）和成年大脑中的 T3 含量，以及调节棕色脂肪组织（BAT）中的适应性产热。然而，DIO2 的鉴定和克隆一直具有挑战性。近年来，几项临床研究集中在 Thr92Ala 多态性上，该多态性与 2 型糖尿病、肥胖症、高血压和骨关节炎等临床综合征密切相关。Thr92Ala-DIO2 也与骨骼和神经退行性疾病和肿瘤有关。然而，在过去 5 年中，相对较少的综述综合了个体脱碘酶，特别是 DIO2 的研究。本文综述了目前关于 DIO2 在甲状腺激素信号转导和 BAT 及大脑中的适应性产热中的生理功能的知识，以及 Thr92Ala-DIO2 与骨骼和神经退行性疾病和肿瘤之间的关联。这一讨论有望深入了解 DIO2 的生理功能以及与 Thr92Ala-DIO2 相关的临床综合征。
