Endocrinology and Metabolism

Review Articles

Thyroid
The Physiological Functions and Polymorphisms of Type II Deiodinase: Yan Deng, Yi Han, Sheng Gao, Wei Dong, Yang Yu; Endocrinol Metab. 2023;38(2):190-202. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2022.1599

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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.

Citations

Citations to this article as recorded by

Noncatalytic Reductive Deiodination of Thyroid Hormones. Electrochemistry and Quantum Chemical Calculations
Piotr P. Romańczyk, Stefan S. Kurek
ChemElectroChem.2024;[Epub] CrossRef

Thyroid
Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions: Laura Sabatino, Cristina Vassalle, Cristina Del Seppia, Giorgio Iervasi; Endocrinol Metab. 2021;36(5):952-964. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1198

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Abstract PDF PubReader ePub

Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of the biologically active triiodothyronine (T3) and regulates TH homeostasis at the local level, in a cell- and time-dependent manner. Three deiodinases have been identified—namely iodothyronine deiodinase 1 (DIO1), DIO2, and DIO3—that differ in their catalytic properties and tissue distribution. The deiodinases represent a dynamic system that changes in the different stages of life according to their functions and roles in various cell types and tissues. Deiodinase activity at the tissue level permits cell-targeted fine regulation of TH homeostasis, mediating the activation (DIO1 and DIO2) and inactivation (DIO3) of THs. Deiodinase homeostasis is the driving force that leads T3-target cells towards customized TH signaling, which takes into account both the hormonal circulating levels and the tissue-specific response. This review analyzes the complex role of deiodinases in physiological and pathological contexts, exploring new challenges and opportunities deriving from a deeper knowledge of the dynamics underlying their roles and functions.

Citations

Citations to this article as recorded by

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Original Article

Vitamin D Receptor Gene 3' End Polymorphisms in Patients with Graves' Disease in Koreans.: Jae Kyung Hwang, Kyung Won Kim, Tae Yong Kim, Hui Su Lee, Young Joo Park, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Byung Doo Rhee, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2003;18(1):12-23. Published online February 1, 2003

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Abstract PDF: BACKGROUND
The aim of this study was to evaluate the association of vitamin D receptor (VDR) gene polymorphisms with Graves' disease in Koreans. We also investigated the association of VDR gene polymorphisms with the clinical characteristics and titers of TSH receptor antibodies in patients with Graves' disease. SUBJECTS AND METHODS: The VDR gene polymorphisms were evaluated in 117 patients with Graves' disease and 156 normal controls. The polymorphisms were represented according to restriction fragment length polymorphism; Aa(ApaI), Bb(BsmI) and Tt(TaqI), with the capital letters signifying the absence, and small letters the presence of restriction sites. RESULTS: The distribution of the ApaI polymorphism genotype was: AA(17.1%), Aa(50.4%) and aa(32.5%). The BsmI polymorphism genotype distribution was: BB(7.1%), Bb(35.4%) and bb(57.5%); and the TaqI polymorphism genotype distribution was: TT(92.6%), Tt(6.2) and tt(1.2%). No significant differences in either genotypic or allelic distributions were observed, between the patients with Graves' disease and the normal controls, associated with the VDR gene polymorphisms. No significant differences were observed with age, sex, size of goiter or the presence of ophthalmopathy, in patients with Graves' disease associated with the VDR gene polymorphisms. However, the titers of the TBII were significantly higher in the aa than the Aa genotype, and were also higher in the group without the A allele than in groups with(aa 55.9+/-18.3 vs. Aa 43.2+/-23.4, p<0.05; aa 55.9+/-18.3 vs. AA and Aa 42.9+/-23.5, p<0.05). Thyroid stimulating antibodies measured with a CHO cell transfected with a wild type of human TSH receptor, were also higher in patients without the A allele than in those with(aa 620+/-829 vs. AA and Aa 353+/-306, p<0.05). The titers of the anti-thyroglobulin antibodies were significantly higher in the groups not containing the B allele than in the group that did(bb 50.9+/-42.8 vs. BB and Bb 31.9+/-38.9, p<0.05). The serum alkaline phosphatase activities were higher in the group having the b allele than in the group that did not(Bb and bb 139+/-68 vs. BB 82.2+/-15.5, p<0.05). CONCLUSIONS: The VDR gene 3' end polymorphism was not associated with susceptibility to Graves' disease in Koreans. The studies of other polymorphism sites of the VDR gene might be required to elucidate the association of VDR gene polymorphisms with Graves' disease in Koreans.

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