Preview

Problems of Endocrinology

Advanced search

Role of type 1 and 2 deiodinases in thyroid metabolism (review)

https://doi.org/10.14341/probl201662246-52

Abstract

Thyroid hormones control growth, development and metabolism in animals. The iodothyronine deiodinases catalyze the removal of an iodine residue from outer or inner ring of the pro-hormone thyroxin (T4) molecule, thus producing either the active form triiodothyronine (T3; activation) or inactive metabolites (reverse T3; inactivation), respectively. Type 1 deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on thyroid metabolism in physiology and pathology. Type 2 deiodinase (D2) initiates thyroid hormone signaling by activating the T4 to the biologically active T3 molecule followed by gene expression on a cell-specific basis. Expression of D2 in such specific tissues as hypothalamus, pitutary, brain, brown adipose tissue, cochlea, retina, skeleton demonstrates the role of enzyme in physiology of these organs suggesting further therapeutic application. The current review intended to provide an updated picture of the recent advances concerning the molecular properties of D1 and D2 as well as their role in physiology.

About the Author

Gulnora M. Artykbaeva
Institute of Bioorganic chemistry named after acad. A.S. Sadykov
Uzbekistan
PhD
Competing Interests: нет конфликта интересов


References

1. Gereben B, Zavacki Am, Ribich S, et al. Cellular And Molecular Basis Of Deiodinase-Regulated Thyroid Hormone Signaling1. Endocr Rev. 2008;29(7):898-938. doi: 10.1210/er.2008-0019.

2. Friesema ECH, Kuiper GGJM, Jansen J, et al. Thyroid Hormone Transport By The Human Monocarboxylate Transporter 8 And Its Rate-Limiting Role In Intracellular Metabolism. Mol Endocrinol. 2006;20(11):2761-2772. doi: 10.1210/Me.2005-0256.

3. Dumitrescu AM, Liao X-H, Weiss RE, et al. Tissue-Specific Thyroid Hormone Deprivation And Excess In Monocarboxylate Transporter (Mct) 8-Deficient Mice. Endocrinology. 2006;147(9): 4036-4043. doi: 10.1210/en.2006-0390.

4. Heuer H. The importance of thyroid hormone transporters for brain development and function. Best Pract Res Clin Endocrinol Metab. 2007;21(2):265-276. doi: 10.1016/j.beem.2007.03.003.

5. Van Der Deure WM, Peeters RP, Visser TJ. Molecular aspects of thyroid hormone transporters, including MCT8, MCT10, and OATPS, and the effects of genetic variation in these transporters. J Mol Endocrinol. 2010;44(1):1-11. doi: 10.1677/JME-09-0042.

6. Berry Mj, Grieco D, Taylor Ba, et al. Physiological and genetic analyses of inbred mouse strains with a type i iodothyronine 5’ deiodinase deficiency. J Clin Invest. 1993;92(3):1517-1528. doi: 10.1172/JCI116730.

7. Wagner Ms, Wajner Sm, Maia Al. The role of thyroid hormone in testicular development and function. J Endocrinol. 2008;199(3):351-365.doi: 10.1677/JOE-08-0218.

8. Kester MH, Martinez De Mena R, Obregon MJ, et al. Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas. J Clin Endocrinol Metab. 2004;89(7):3117-3128. doi: 10.1210/Jc.2003-031832.

9. Bianco AC, Maia AL, Da Silva WS, Christoffolete MA. Adaptive activation of thyroid hormone and energy expenditure. Biosci Rep. 2005;25(3-4):191-208.doi: 10.1007/s10540-005-2885-6.

10. Maia AL, Kim BW, Huang SA, et al. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest. 2005;115(9):2524-2533. doi: 10.1172/Jci25083.

11. Baqui MM, Gereben B, Harney JW, et al. Distinct subcellular localization of transiently expressed types 1 and 2 iodothyronine deiodinases as determined by immunofluorescence confocal microscopy. Endocrinology. 2000;141(11):4309-4312. doi: 10.1210/endo.141.11.7872.

12. Arrojo EDR, Bianco AC. Type 2 deiodinase at the crossroads of thyroid hormone action. Int J Biochem Cell Biol. 2011;43(10):1432-1441. doi: 10.1016/j.biocel.2011.05.016.

13. Schneider MJ, Fiering SN, Thai B, et al. Targeted disruption of thee Type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology. 2006;147(1):580-589. doi: 10.1210/en.2005-0739.

14. Maia AL, Goemann IM, Meyer EL, Wajner SM. Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease. J Endocrinol. 2011;209(3):283-297. doi: 10.1530/JOE-10-0481.

15. Wagner MS, Wajner SM, Dora JM, Maia AL. Regulation of Dio2 gene expression by thyroid hormones in normal and Type 1 deiodinase-deficient C3h mice. J Endocrinol. 2007;193(3):435-444. doi: 10.1677/JOE-07-0099.

16. Galton VA, Schneider MJ, Clark AS, St Germain DL. Life without thyroxine to 3,5,3’-triiodothyronine conversion: studies in mice devoid of the 5’-deiodinases. Endocrinology. 2009;150(6):2957-2963. doi: 10.1210/en.2008-1572.

17. Scanlan TS, Suchland KL, Hart ME, et al. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med. 2004;10(6):638-642. doi: 10.1038/nm1051.

18. Piehl S, Heberer T, Balizs G, et al. Thyronamines are isozyme-specific substrates of deiodinases. Endocrinology. 2008;149(6):3037-3045. doi: 10.1210/en.2007-1678.

19. Scanlan TS. Minireview: 3-Iodothyronamine (T1AM): a new player on the thyroid endocrine team? Endocrinology. 2009;150(3):1108-1111. doi: 10.1210/en.2008-1596.

20. Schneider MJ, Fiering SN, Pallud SE, et al. Targeted disruption of the Type 2 selenodeiodinase gene (Dio2) results in a phenotype of pituitary resistance to T4. Mol Endocrinol. 2001;15(12):2137-2148. doi: 10.1210/mend.15.12.0740.

21. De Jesus LA, Carvalho SD, Ribeiro MO, et al. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest. 2001;108(9):1379-1385. doi: 10.1172/jci200113803.

22. Bassett JH, Boyde A, Howell PG, et al. Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts. Proc Natl Acad Sci USA. 2010;107(16):7604-7609. doi: 10.1073/pnas.0911346107.

23. Christoffolete MA, Arrojo E, Drigo R, Gazoni F, et al. Mice with impaired extrathyroidal thyroxine to 3,5,3′-triiodothyronine conversion maintain normal serum 3,5,3′-triiodothyronine concentrations. Endocrinology. 2007;148(3):954-960. doi: 10.1210/en.2006-1042.

24. Rosene ML, Wittmann G, Arrojo E Drigo R, et al. Inhibition of the Type 2 iodothyronine deiodinase underlies tht elevated plasma TSH associated with amiodarone treatment. Endocrinology. 2010;151(12):5961-5970. doi: 10.1210/en.2010-0553.

25. Williams GG, Bassett JH. Deiodinases: the balance of thyroid hormone: local control of thyroid hormone action: role of Type 2 deiodinase. J Endocrinol. 2011;209(3):261-272. doi: 10.1530/JOE-10-0448.

26. Galton VA, Wood ET, St Germain EA, et al. Thyroid hormone homeostasis and action in the Type 2 deiodinase-deficient rodent brain during development. Endocrinology. 2007;148(7):3080-3088. doi: 10.1210/en.2006-1727.

27. Verhoelst CH, Darras VM, Roelens SA, et al. Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain. J Endocrinol. 2004;183(1):235-241. doi: 10.1677/joe.1.05743.

28. Morte B, Ceballos A, Diez D, et al. Thyroid hormone-regulated mouse cerebral cortex genes are differentially dependent on the source of the hormone: a study in monocarboxylate transporter-8- and deiodinase-2-deficient mice. Endocrinology. 2010;151(5):2381-2387. doi: 10.1210/en.2009-0944.

29. Christoffolete MA, Linardi CCG, De Jesus L, et al. Mice with targeted disruption of the Dio2 gene have cold-induced overexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis. Diabetes. 2004;53(3):577-584. doi: 10.2337/diabetes.53.3.577.

30. Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484-489. doi: 10.1038/nature04330.

31. Hall JA, Ribich S, Christoffolete MA, et al. Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. Endocrinology. 2010;151(9):4573-4582. doi: 10.1210/en.2010-0511.

32. Marsili A, Ramadan W, Harney JW, et al. Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism. Endocrinology. 2010;151(12):5952-5960. doi: 10.1210/En.2010-0631.

33. Dentice M, Marsili A, Ambrosio R, et al. The Foxo3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. J Clin Invest. 2010;120(11):4021-4030. doi: 10.1172/jci43670.

34. Campos-Barros A, Amma LL, Faris JS, et al. Type 2 iodothyronine deiodinase expression in the cochlea before the onset of hearing. Proceedings of the National Academy of Sciences. 2000;97(3):1287-1292. doi: 10.1073/pnas.97.3.1287.

35. Rusch A, Ng L, Goodyear R, et al. Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors. J Neurosci. 2001;21(24):9792-9800.

36. Dentice M, Bandyopadhyay A, Gereben B, et al. The hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHRP secretion in the developing growth plate. Nat Cell Biol. 2005;7(7):698-705. doi: 10.1038/ncb1272.

37. Dentice M, Marsili A, Zavacki A, et al. The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation. Biochim Biophys Acta. 2013;1830(7):3937-3945. doi: 10.1016/j.bbagen.2012.05.007.

38. Stevens DA, Hasserjian RP, Robson H, et al. Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation. J Bone Miner Res. 2000;15(12):2431-2442. doi: 10.1359/jbmr.2000.15.12.2431.

39. Williams AJ, Robson H, Kester MH, et al. Iodothyronine deiodinase enzyme activities in bone. Bone. 2008;43(1):126-134. doi: 10.1016/j.bone.2008.03.019.

40. Bassett JH, Boyde A, Howell PG, et al. Optimal bone strength and mineralization requires the Type 2 iodothyronine deiodinase in osteoblasts. Proc Natl Acad Sci USA. 2010;107(16):7604-7609. doi: 10.1073/pnas.0911346107.

41. Wojcicka A, Bassett JH, Williams GG. Mechanisms of action of thyroid hormones in the skeleton. Biochim Biophys Acta. 2013;1830(7):3979-3986. doi: 10.1016/j.bbagen.2012.05.005.

42. Gouveia CH, Christoffolete MA, Zaitune CR, et al. Type 2 iodothyronine selenodeiodinase in expressed throughout the mouse skeleton and in the MC3T3-E1 mouse osteoblastic cell line during differentiation. Endocrinology. 2005;146(1):195-200. doi: 10.1210/En.2004-1043.

43. Vestergaard P, Rejnmark L, Mosekilde L. Influence of hyper- and hypothyroidism, and the effects of treatment with antithyroid drugs and levothyroxine on fracture risk. Calcif Tissue Int. 2005;77(3):139-144. doi: 10.1007/S00223-005-0068-x.

44. Meulenbelt I, Min JL, Bos S, et al. Identification of Dio2 as a new susceptibility locus for symptomatic osteoarthritis. Hum Mol Genet. 2008;17(12):1867-1875. doi: 10.1093/hmg/ddn082.

45. Kerkhof HJM, Lories RJ, Meulenbelt I, et al. A genome-wide association study identifies a locus on chromosome 7q22 to influence susceptibility for osteoarthritis. Arthritis Rheum. 2010:NA-NA. doi: 10.1002/art.27184.

46. Yoshimura T, Yasuo S, Watanabe M, et al. Light-induced hormone conversion of T4 to T3 regulates photoperiodic response of gonads in birds. Nature. 2003;426(6963):178-181. doi: 10.1038/nature02117.

47. Nakao N, Ono H, Yamamura T, et al. Thyrotrophin in the pars tuberalis triggers photoperiodic response. Nature. 2008;452(7185):317-322. doi: 10.1038/nature06738.

48. Watanabe M, Yasuo S, Watanabe T, et al. Photoperiodic regulation of Type 2 deiodinase gene in djungarian hamster: possible homologies between avian and mammalian photoperiodic regulation of reproduction. Endocrinology. 2004;145(4):1546-1549. doi: 10.1210/en.2003-1593.

49. Hanon EA, Lincoln GA, Fustin J-M, et al. Ancestral TSH mechanism signals summer in a photoperiodic Mammal. Curr Biol. 2008;18(15):1147-1152. doi: 10.1016/j.cub.2008.06.076.

50. Ono H, Hoshino Y, Yasuo S, et al. Involvement of thyrotropin in photoperiodic signal transduction in mice. Proceedings of the National Academy of Sciences. 2008;105(47):18238-18242. doi: 10.1073/pnas.0808952105.

51. Yoshimura T. Neuroendocrine mechanism of seasonal reproduction in birds and mammals. Animal Science Journal. 2010;81(4):403-410. doi: 10.1111/j.1740-0929.2010.00777.x.

52. Wood S, Loudon A. Clocks for all seasons: unwinding the roles and mechanisms of circadian and interval timers in the hypothalamus and pituitary. J Endocrinol. 2014;222(2):R39-R59. doi: 10.1530/Joe-14-0141.

53. Galton VA, De Waard E, Parlow AF, et al. Life without the iodothyronine deiodinases. Endocrinology. 2014;155(10):4081-4087. doi: 10.1210/en.2014-1184.

54. Darras VM, Van Herck SLJ. Iodothyronine deiodinase structure and function: from ascidians to humans. J Endocrinol. 2012;215(2):189-206. doi: 10.1530/joe-12-0204.


Supplementary files

1. Рис.1. Метаболизм основных йодотиронинов
Subject
Type Other
View (8MB)    
Indexing metadata ▾
2. Рис.2. Роль DIO2 в механизме обратной регуляции ГГТ оси
Subject
Type Other
View (10MB)    
Indexing metadata ▾

Review

For citations:


Artykbaeva G.M. Role of type 1 and 2 deiodinases in thyroid metabolism (review). Problems of Endocrinology. 2016;62(2):46-52. https://doi.org/10.14341/probl201662246-52

Views: 5496


ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)