Endocrinol Metab.  2023 Apr;38(2):190-202. 10.3803/EnM.2022.1599.

The Physiological Functions and Polymorphisms of Type II Deiodinase

• Deng Y
• Han Y
• Gao S
• Dong W
• Yu Y

• KMID: 2541875
• DOI: http://doi.org/10.3803/EnM.2022.1599

Abstract

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.

Keyword

Deiodinases; Iodothyronine deiodinase type II; Physiological functions; Polymorphisms; Thr92Ala

Figure

• 

  Fig. 1. Schematic representation of the genomic actions of type II deiodinase (DIO2) in target cells, taking adipocytes as an example, as well as the occurrence of bone diseases caused by the Thr92Ala polymorphism in DIO2. Thyroxine (T4) is secreted by the thyroid gland and transported to the target tissue, such as adipose tissue (AT), through the blood. T4 then enters the cell via transport proteins including monocarboxylate transporter 8 (MCT8), MCT10, and organic anion-transporting polypeptide 1C1 (OATP1C1), which are located on the plasma and nuclear membranes. In the cytoplasm, DIO2 located in the endoplasmic reticulum catalyzes the conversion of T4 into active triiodothyronine (T3). Active T3 enters the nucleus via transport proteins and binds to thyroid hormone receptors (TRs) to regulate gene expression. However, when the subcellular location of DIO2 is in the Golgi apparatus in osteocytes, and the amino acid at position 92 of DIO2 changes from T (threonine) into A (alanine), bone diseases, such as osteoarthritis, osteoporosis, and Kashin-Beck disease (KBD), will occur. TRE, transcriptional regulatory element.

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