Роль дейодиназ 1-го и 2-го типа в метаболизме тиреоидных гормонов (обзор литературы)

Тиреоидные гормоны контролируют рост, развитие и обмен веществ организма. Дейодиназы йодтиронинов катализируют удаление остатка йода с внешнего или внутреннего кольца молекулы прогормона тироксина (Т4), продуцируя либо активную (Т3), либо неактивную (обратный Т3, оТ3) форму трийодтиронина. Дейодиназа 1-го типа (Д1) катализирует обе эти реакции. Дейодиназа 2-го типа (Д2) образует из Т4 активный Т3 внутри клетки, инициируя тем самым передачу гормонального сигнала на генетический аппарат клеток. Экспрессия Д2 в отдельных тканях (гипоталамус, гипофиз, бурая жировая ткань, улитка внутреннего уха, сетчатка глаза, кость и некоторые другие) свидетельствует о роли фермента в развитии этих органов. В обзоре описаны последние достижения в области изучения молекулярных свойств Д1 и Д2, а также их роли в физиологии.

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.