Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Journal of Endocrinological Investigation

Volumn 34, Issue 5, 2011, Pages 395-407

  Marsili, A ^a   Zavacki, A M ^a   Harney, J W ^a   Larsen, P R ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Deiodinase; Hyperthyroidism; Hypothyroidism; Iodine; Nonthyroidal illness; Selenium; Selenoprotein; Thyroid hormone action; Thyroid hormone metabolism; Thyroxine; Triiodothyronine; TSH

Indexed keywords

IMATINIB; IODIDE; IODOTHYRONINE DEIODINASE 1; IODOTHYRONINE DEIODINASE 2; IODOTHYRONINE DEIODINASE 3; IOPODATE SODIUM; LIOTHYRONINE; MOTESANIB; PROPYLTHIOURACIL; SELENOPROTEIN; SORAFENIB; THIAMAZOLE; THYROXINE; THYROXINE DEIODINASE; UNCLASSIFIED DRUG;

BONE METABOLISM; DIIODOTHYRONINE DEIODINASE; ENZYME REGULATION; FEEDBACK SYSTEM; GENETIC MODEL; HALF LIFE TIME; HOMEOSTASIS; HUMAN; HYPERTHYROIDISM; HYPOTHYROIDISM; IODINE DEFICIENCY; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; THYROID CARCINOMA; THYROTOXICOSIS; TISSUE REPAIR;

ANIMALS; FEEDBACK, PHYSIOLOGICAL; HUMANS; IODIDE PEROXIDASE; MOLECULAR STRUCTURE; THYROID DISEASES; THYROID GLAND; THYROXINE; TRIIODOTHYRONINE;

EID: 79960231753     PISSN: 03914097     EISSN: 17208386     Source Type: Journal    
DOI: 10.3275/7615     Document Type: Review

References (134)

1. Berry MJ, Maia AL, Kieffer JD, Harney JW, Larsen PR. Substitution of cysteine for selenocysteine in type I iodothyronine deiodinase reduces the catalytic efficiency of the protein but enhances its translation. Endocrinology 1992, 131: 1848-52.
2. Berry MJ, Banu L, Chen YY, et al. Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3' untranslated region. Nature 1991, 353: 273-6. (Pubitemid 21896772)
3. Berry MJ. Knowing when not to stop. Nat Struct Mol Biol 2005, 12: 389-90. (Pubitemid 43085895)
4. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 2002, 23: 38-89. (Pubitemid 34185306)
5. Gereben B, Zavacki AM, Ribich S, et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev 2008, 29: 898-938.
6. Silva JE, Larsen PR Pituitary nuclear 3,5,3′-triiodothyronine and thyrotropin secretion: an explanation for the effect of thyroxine. Science 1977, 198: 617-20.
7. Larsen PR. Thyroid-pituitary interaction: feedback regulation of thyrotropin secretion by thyroid hormones. N Engl J Med 1982, 306: 23-32.
8. Larsen PR, Dick TE, Markovitz BP, Kaplan MM, Gard TG. Inhibition of intrapituitary thyroxine to 3.5.3′-triiodothyronine conversion prevents the acute suppression of thyrotropin release by thyroxine in hypothyroid rats. J Clin Invest 1979, 64: 117-28. (Pubitemid 9216526)
9. Silva JE, Larsen PR. Peripheral metabolism of homologous thyrotropin in euthyroid and hypothyroid rats: acute effects of thyrotropin-releasing hormone, triiodothyronine, and thyroxine. Endocrinology 1978, 102: 1783-96. (Pubitemid 8376438)
10. Connors JM, Hedge GA. Feedback effectiveness of periodic versus constant triiodothyronine replacement. Endocrinology 1980, 106: 911-7. (Pubitemid 10135128)
11. Christoffolete MA, Ribeiro R, Singru P, et al. Atypical expression of type 2 iodothyronine deiodinase in thyrotrophs explains the thyroxine-mediated pituitary thyrotropin feedback mechanism. Endocrinology 2006, 147: 1735-43.
12. Larsen PR, Silva JE, Kaplan MM. Relationships between circulating and intracellular thyroid hormones: physiological and clinical implications. Endocr Rev 1981, 2: 87-102.
13. Schneider MJ, Fiering SN, Pallud SE, Parlow AF, St Germain DL, Galton VA. Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol Endocrinol 2001, 15: 2137-48. (Pubitemid 33141133)
14. Segerson TP, Kauer J, Wolfe HC, et al. Thyroid hormone regulates TRH biosynthesis in the paraventricular nucleus of the rat hypothalamus. Science 1987, 238: 78-80. (Pubitemid 17150486)
15. Kakucska I, Rand W, Lechan RM. Thyrotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus is dependent upon feedback regulation by both triiodothyronine and thyroxine. Endocrinology 1992, 130: 2845-50.
16. Riskind PN, Kolodny JM, Larsen PR. The regional hypothalamic distribution of type II 5′-monodeiodinase in euthyroid and hypothyroid rats. Brain Res 1987, 420: 194-8. (Pubitemid 17151318)
17. Tu HM, Kim SW, Salvatore D, et al. Regional distribution of type 2 thyroxine deiodinase messenger ribonucleic acid in rat hypothalamus and pituitary and its regulation by thyroid hormone. Endocrinology 1997, 138: 3359-68. (Pubitemid 27345689)
18. Izumi M, Larsen PR Triiodothyronine, thyroxine, and iodine in purified thyroglobulin from patients with Graves' disease. J Clin Invest 1977, 59: 1105-12.
19. Salvatore D, Tu H, Harney JW, Larsen PR Type 2 iodothyronine deiodinase is highly expressed in human thyroid. J Clin Invest 1996, 98: 962-8. (Pubitemid 26293314)
20. Laurberg P. Mechanisms governing the relative proportions of thyroxine and 3,5,3′-triiodothyronine in thyroid secretion. Metabolism 1984, 33: 379-92.
21. Pilo A, lervasi G, Vitek F, Ferdeghini M, Cazzuola F, Bianchi R. Thyroidal and peripheral production of 3,5,3′-triiodothyronine in humans by muiticompartmental analysis. Am J Physiol 1990, 258: E715-26.
22. Saberi M, Sterling FH, Utiger RD. Reduction in extrathyroidal triiodothyronine production by propylthiouracil in man. J Clin Invest 1975, 55: 218-23.
23. Maia AL, Kim BW, Huang SA, Harney JW, Larsen PR. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest 2005, 115: 2524-33. (Pubitemid 41266215)
24. Lum SM, Nicoloff JT, Spencer CA, Kaptein EM. Peripheral tissue mechanism for maintenance of serum triiodothyronine values in a thyroxine-deficient state in man. J Clin Invest 1984, 73: 570-5. (Pubitemid 14194639)
25. Steinsapir J, Bianco AC, Buettner C, Harney J, Larsen PR. Substrate-induced down-regulation of human type 2 deiodinase (hD2) is mediated through proteasomal degradation and requires interaction with the enzyme's active center. Endocrinology 2000, 141: 1127-35. (Pubitemid 32260455)
26. Gereben B, Goncalves C, Harney JW, Larsen PR, Bianco AC. Selective proteolysis of human type 2 deiodinase: a novel ubiquitin-proteasomal mediated mechanism for regulation of hormone activation. Mol Endocrinol 2000, 14: 1697-708.
27. Burmeister LA, Pachucki J, St Germain DL. Thyroid hormones inhibit type 2 iodothyronine deiodinase in the rat cerebral cortex by both pre-and posttranslational mechanisms. Endocrinology 1997, 138: 5231-7. (Pubitemid 27509683)
28. Silva JE, Matthews PS. Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism. J Clin Invest 1984, 74: 1035-49. (Pubitemid 14031044)
29. Peeters RP, Friesema EC, Docter R, Hennemann G, Visser TJ. Effects of thyroid state on the expression of hepatic thyroid hormone transporters in rats. Am J Physiol Endocrinol Metab 2002, 283: E1232-8.
30. 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: 2957-63.
31. Porterfield SP, Hendrich CE. The role of thyroid hormones in prenatal and neonatal neurological development - current perspectives. Endocr Rev 1993, 14: 94-106. (Pubitemid 23066534)
32. Bernai J. Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab 2007, 3: 249-59.
33. Heuer H, Visser TJ. Minireview: Pathophysiological importance of thyroid hormone transporters. Endocrinology 2009, 150: 1078-83.
34. Guadano-Ferraz A, Obregon MJ, St Germain DL, Bernai J. The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain. Proc Natl Acad Sci U S A 1997, 94: 10391-6. (Pubitemid 27407052)
35. Peeters R, Fekete C, Goncalves C, et al. Regional physiological adaptation of the central nervous system deiodinases to iodine deficiency. Am J Physiol Endocrinol Metab 2001, 281: E54-61.
36. 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: 2381-7.
37. Hernandez A, Quignodon L, Martinez ME, Flamant F, St Germain DL. Type 3 deiodinase deficiency causes spatial and temporal alterations in brain T3 signaling that are dissociated from serum thyroid hormone levels. Endocrinology 2010, 151: 5550-8.
38. Fekete C, Gereben B, Doleschall M, et al. Lipopolysaccharide induces type 2 iodothyronine deiodinase in the mediobasal hypothalamus: implications for the nonthyroidal illness syndrome. Endocrinology 2004, 145: 1649-55. (Pubitemid 38402371)
39. Freitas BC, Gereben B, Castillo M, et al. Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells. J Clin Invest 2010, 120: 2206-17.
40. Ng L, Hernandez A, He W, et al. A protective role for type 3 deiodinase, a thyroid hormone-inactivating enzyme, in cochlear development and auditory function. Endocrinology 2009, 150: 1952-60.
41. Campos-Barros A, Amma LL, Paris JS, et al. Type 2 iodothyronine deiodinase expression in the cochlea before the onset of hearing. Proc Natl Acad Sci U S A 2000, 97: 1287-92. (Pubitemid 30080851)
42. Ng L, Goodyear RJ, Woods CA, et al. Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase. Proc Natl Acad Sci U S A 2004, 101: 3474-9. (Pubitemid 38338219)
43. Ng L, Lyubarsky A, Nikonov SS, et al. Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors. J Neurosci 2010, 30: 3347-57.
44. 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: 698-705. (Pubitemid 40975751)
45. Silva JE, Larsen PR. Adrenergic activation of triiodothyronine production in brown adipose tissue. Nature 1983, 305: 712-3. (Pubitemid 13021520)
46. Bianco AC, Silva JE. Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. J Clin Invest 1987, 79: 295-300. (Pubitemid 17232532)
47. 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: 1379-85. (Pubitemid 33107766)
48. Christoffolete MA, Linardi CC, 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: 577-84. (Pubitemid 38270625)
49. Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006, 439: 484-9. (Pubitemid 43152840)
50. al-Adsani H, Hoffer LJ, Silva JE. Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab 1997, 82: 1118-25.
51. Salvatore D, Bartha T, Harney JW, Larsen PR. Molecular biological and biochemical characterization of the human type 2 selenodeiodinase. Endocrinology 1996, 137: 3308-15. (Pubitemid 26250180)
52. Marsili A, Ramadan W, Hamey 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: 5952-60.
53. Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009, 360: 1509-17.
54. Skarulis MC, Celi FS, Mueller E, et al. Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. J Clin Endocrinol Metab 2010, 95: 256-62.
55. Silva JE. Thermogenic mechanisms and their hormonal regulation. Physiol Rev 2006, 86: 435-64.
56. Lopez M, Varela L, Vazquez MJ, et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med 2010, 16: 1001-8.
57. 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 U S A 2010, 107: 7604-9.
58. Canani LH, Capp C, Dora JM, et al. The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2005, 90: 3472-8. (Pubitemid 41014316)
59. Heemstra KA, Hoftijzer H, van der Deure WM, et al. The type 2 deiodinase Thr92Ala polymorphism is associated with increased bone turnover and decreased femoral neck bone mineral density. J Bone Miner Res 2010, 25: 1385-91.
60. Visser WE, Heemstra KA, Swagemakers SM, et al. Physiological thyroid hormone levels regulate numerous skeletal muscle transcripts. J Clin Endocrinol Metab 2009, 94: 3487-96.
61. Heemstra KA, Soeters MR, Fliers E, et al. Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting. J Clin Endocrinol Metab 2009, 94: 2144-50.
62. Larsen PR. Type 2 iodothyronine deiodinase in human skeletal muscle: new insights into its physiological role and regulation. J Clin Endocrinol Metab 2009, 94: 1893-5.
63. Muscat GE, Mynett-Johnson L, Dowhan D, Downes M, Griggs R. Activation of myoD gene transcription by 3,5,3′-triiodo-L-thyronine: a direct role for the thyroid hormone and retinoid X receptors. Nucleic Acids Res 1994, 22: 583-91.
64. 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: 4021-30.
65. Olivares EL, Marassi MP, Fortunato RS, et al. Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study. Endocrinology 2007, 148: 4786-92. (Pubitemid 47481559)
66. Pol CJ, Muller A, Zuidwijk M J, et al. Left-ventricular remodeling after myocardial infarction is associated with a cardiomyocyte-specific hypothyroid condition. Endocrinology 2011, 152: 669-79.
67. Wessen FW, Schiel AE, Kuiper GG, et al. Induction of thyroid hormone-degrading deiodinase in cardiac hypertrophy and failure. Endocrinology 2002, 143: 2812-5. (Pubitemid 34701346)
68. Li WW, Le Goascogne C, Ramauge M, et al. Induction of type 3 iodothyronine deiodinase by nerve injury in the rat peripheral nervous system. Endocrinology 2001, 142: 5190-7. (Pubitemid 33131947)
69. Simonides WS, Mulcahey MA, Redout EM, et al. Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats. J Clin Invest 2008, 118: 975-83. (Pubitemid 351364605)
70. Boelen A, Kwakkel J, Alkemade A, et al. Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation. Endocrinology 2005, 146: 5128-34. (Pubitemid 41653026)
71. Boelen A, Boorsma J, Kwakkel J, et al. Type 3 deiodinase is highly expressed in infiltrating neutrophilic granulocytes in response to acute bacterial infection. Thyroid 2008, 18: 1095-03.
72. Boelen A, Kwakkel J, Wieland CW, et al. Impaired bacterial clearance in type 3 deiodinase-deficient mice infected with Streptococcus pneumoniae. Endocrinology 2009, 150: 1984-90.
73. Abuid J, Larsen PR. Triiodothyronine and thyroxine in hyperthyroidism. Comparison of the acute changes during therapy with antithyroid agents. J Clin Invest 1974, 54: 201-8.
74. Nishikawa M, Toyoda N, Yonemoto T, et al. Quantitative measurements for type 1 deiodinase messenger ribonucleic acid in human peripheral blood mononuclear cells: mechanism of the preferential increase of T3 in hyperthyroid Graves' disease. Biochem Biophys Res Commun 1998, 250: 642-6. (Pubitemid 28484781)
75. Ishii H, Inada M, Tanaka K, et al. Triiodothyronine generation from thyroxine in human thyroid: enhanced conversion in Graves' thyroid tissue. J Clin Endocrinol Metab 1981, 52: 1211-7. (Pubitemid 13237527)
76. Toyoda N, Nishikawa M, Horimoto M, et al. Graves' immunoglobulin G stimulates iodothyronine 5′-deiodinating activity in FRTL-5 rat thyroid cells. J Clin Endocrinol Metab 1990, 70: 1506-11.
77. Geffner DL, Azukizawa M, Hershman JM. Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man. J Clin Invest 1975, 55: 224-9.
78. Laurberg P, Vestergaard H, Nielsen S, et al. Sources of circulating 3,5,3′-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases. J Clin Endocrinol Metab 2007, 92: 2149-56.
79. Ito M, Toyoda N, Nomura E, et al. Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with 3,5,3′-triiodothyronine- predominant Graves' disease. Eur J Endocrinol 2011, 164: 95-100.
80. Huang SA, Tu HM, Hamey JW, et al. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med 2000, 343: 185-9. (Pubitemid 30489216)
81. Ruppe MD, Huang SA, Jan de Beur SM. Consumptive hypothyroidism caused by paraneoplastic production of type 3 iodothyronine deiodinase. Thyroid 2005, 15: 1369-72. (Pubitemid 43132684)
82. Huang SA, Fish SA, Dorfman DM, et al. A 21-year-old woman with consumptive hypothyroidism due to a vascular tumor expressing type 3 iodothyronine deiodinase. J Clin Endocrinol Metab 2002, 87: 4457-61. (Pubitemid 35247024)
83. Kim BW, Daniels GH, Harrison BJ, et al. Overexpression of type 2 iodothyronine deiodinase in follicular carcinoma as a cause of low circulating free thyroxine levels. J Clin Endocrinol Metab 2003, 88: 594-8. (Pubitemid 36207796)
84. Celi FS, Coppotelli G, Chidakel A, et al. The role of type 1 and type 2 5′-deiodinase in the pathophysiology of the 3,5,3′-triiodothyronine toxicosis of McCune-Albright syndrome. J Clin Endocrinol Metab 2008, 93: 2383-9.
85. Adler SM, Wartofsky L. The nonthyroidal illness syndrome. Endocrinol Metab Clin North Am 2007, 36: 657-72, vi.
86. Peeters RP, Wouters PJ, van Toor H, et al. Serum 3,3′,5′- triiodothyronine (rT3) and 3,5,3′-triiodothyronine/rT3 are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities. J Clin Endocrinol Metab 2005, 90: 4559-65.
87. Yu J, Koenig RJ. Regulation of hepatocyte thyroxine 5′-deiodinase by T3 and nuclear receptor coactivators as a model of the sick euthyroid syndrome. J Biol Chem 2000, 275: 38296-301. (Pubitemid 32009151)
88. Debaveye Y, Ellger B, Mebis L, et al. Tissue deiodinase activity during prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone-releasing peptide-2. Endocrinology 2005, 146: 5604-11. (Pubitemid 41653077)
89. Rodriguez-Perez A, Palos-Paz F, Kaptein E, et al. Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock. Clin Endocrinol (Oxf) 2008, 68: 821-7. (Pubitemid 351533438)
90. Mebis L, Langouche L, Visser TJ, Van den Berghe G. The type II iodothyronine deiodinase is up-regulated in skeletal muscle during prolonged critical illness. J Clin Endocrinol Metab 2007, 92: 3330-3. (Pubitemid 47236410)
91. Sanchez E, Singru PS, Wittmann G, et al. Contribution of TNF-alpha and nuclear factor-kappaB signaling to type 2 iodothyronine deiodinase activation in the mediobasal hypothalamus after lipopolysaccharide administration. Endocrinology 2010, 151: 3827-35.
92. Lamirand A, Ramauge M, Pierre M, Courtin F. Bacterial lipopolysaccharide induces type 2 deiodinase in cultured rat astrocytes. J Endocrinol 2010, 208: 183-92.
93. Brent GA, Hershman JM. Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. J Clin Endocrinol Metab 1986, 63: 1-8. (Pubitemid 16093000)
94. Huang SA, Dorfman DM, Genest DR, Salvatore D, Larsen PR. Type 3 iodothyronine deiodinase is highly expressed in the human uteroplacental unit and in fetal epithelium. J Clin Endocrinol Metab 2003, 88: 1384-8. (Pubitemid 36337804)
95. Galton VA, Martinez E, Hernandez A, St Germain EA, Bates JM, St Germain DL. Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase. J Clin Invest 1999, 103: 979-87. (Pubitemid 29169605)
96. Hidal JT, Kaplan MM. Characteristics of thyroxine 5′-deiodination in cultured human placental cells. Regulation by iodothyronines. J Clin Invest 1985, 76: 947-55. (Pubitemid 16225588)
97. Santini F, Chiovato L, Ghirri P, et al. Serum iodothyronines in the human fetus and the newborn: evidence for an important role of placenta in fetal thyroid hormone homeostasis. J Clin Endocrinol Metab 1999, 84: 493-8. (Pubitemid 29075674)
98. Ferreiro B, Bernai J, Goodyer CG, Branchard CL. Estimation of nuclear thyroid hormone receptor saturation in human fetal brain and lung during early gestation. J Clin Endocrinol Metab 1988, 67: 853-6.
99. van Wassenaer AG, Kok JH, de Vijlder JJ, et al. Effects of thyroxine supplementation on neurologic development in infants bom at less than 30 weeks' gestation. N Engl J Med 1997, 336: 21-6. (Pubitemid 26428283)
100. Galton VA, Martinez E, Hernandez A, St Germain EA, Bates JM, St Germain DL. The type 2 iodothyronine deiodinase is expressed in the rat uterus and induced during pregnancy Endocrinology 2001, 142: 2123-8.
101. Huang SA, Mulcahey MA, Crescenzi A, et al. Transforming growth factor-beta promotes inactivation of extracellular thyroid hormones via transcriptional stimulation of type 3 iodothyronine deiodinase. Mol Endocrinol 2005, 19: 3126-36. (Pubitemid 41697726)
102. Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med 2001, 344: 1743-9. (Pubitemid 32497028)
103. Hernandez A, Martinez ME, Fiering S, Galton VA, St Germain D. Type 3 deiodinase is critical for the maturation and function of the thyroid axis. J Clin Invest 2006, 116: 476-84. (Pubitemid 43228365)
104. Hernandez A, Martinez ME, Liao XH, et al. Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis. Endocrinology 2007, 148: 5680-7. (Pubitemid 350146190)
105. Kempers MJ, van Trotsenburg AS, van Tijn DA, et al. Disturbance of the fetal thyroid hormone state has long-term consequences for treatment of thyroidal and central congenital hypothyroidism. J Clin Endocrinol Metab 2005, 90: 4094-100. (Pubitemid 41058178)
106. Dentice M, Ambrosio R, Salvatore D. Role of type 3 deiodinase in cancer. Expert Opin Ther Targets 2009, 13: 1363-73.
107. Santini F, Vitti P, Chiovato L, et al. Role for inner ring deiodination preventing transcutaneous passage of thyroxine. J Clin Endocrinol Metab 2003, 88: 2825-30. (Pubitemid 36724463)
108. Dentice M, Luongo C, Huang S, et al. Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes. Proc Natl Acad Sci U S A 2007, 104: 14466-71. (Pubitemid 350003284)
109. Kester MH, Toussaint MJ, Punt CA, et al. Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver. Endocrinology 2009, 150: 540-5.
110. Norman MF, Lavin TN. Antagonism of thyroid hormone action by amiodarone in rat pituitary tumor cells. J Clin Invest 1989, 83: 306-13. (Pubitemid 19048437)
111. Sogol PB, Hershman JM, Reed AW, Dillmann WH. The effects of amiodarone on serum thyroid hormones and hepatic thyroxine 5′-monodeiodination in rats. Endocrinology 1983, 113: 1464-9. (Pubitemid 13009161)
112. Martino E, Bartalena L, Bogazzi F, Braverman LE. The effects of amiodarone on the thyroid. Endocr Rev 2001, 22: 240-54.
113. Burger A, Dinichert D, Nicod P, Jenny M, Lemarchand-Béraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. A drug influencing peripheral metabolism of thyroid hormones. J Clin Invest 1976, 58: 255-9.
114. Rosene ML, Wittmann G, Arrojo e Drigo R, Singru PS, Lechan RM, Bianco AC. Inhibition of the type 2 iodothyronine deiodinase underlies the elevated plasma TSH associated with amiodarone treat- ment. Endocrinology 2010, 151: 5961-70.
115. Abdulrahman RM, Verloop H, Hoftijzer H, et al. Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination. J Clin Endocrinol Metab 2010, 95: 3758-62.
116. Schoenmakers E, Agostini M, Mitchell C, et al. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J Clin Invest 2010, 120: 4220-35.
117. Dumitrescu AM, Liao XH, Abdullah MS, et al. Mutations in SECIS-BP2 result in abnormal thyroid hormone metabolism. Nat Genet 2005, 37: 1247-52.
118. Di Cosmo C, McLellan N, Liao XH, et al. Clinical and molecular characterization of a novel selenocysteine insertion sequence-binding protein 2 (SBP2) gene mutation (R128X). J Clin Endocrinol Metab 2009, 94: 4003-9.
119. Low SC, Grundner-Culemann E, Harney JW, Berry MJ. SECIS-SBP2 interactions dictate selenocysteine incorporation efficiency and selenoprotein hierarchy. EMBO J 2000, 19: 6882-90. (Pubitemid 32011681)
120. Dumitrescu AM, Di Cosmo C, Liao XH, Weiss RE, Refetoff S. The syndrome of inherited partial SBP2 deficiency in humans. Antioxid Redox Signal 2010, 12: 905-20.
121. Dora JM, Machado WE, Rheinheimer J, Crispim D, Maia AL. Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis. Eur J Endocrinol 2010, 163: 427-34.
122. Maia AL, Hwang SJ, Levy D, Larson MG, Larsen PR, Fox CS. Lack of association between the type 2 deiodinase A/G polymorphism and hypertensive traits: the Framingham Heart Study. Hypertension 2008, 51: e22-3.
123. Gumieniak O, Perlstein TS, Williams JS, et al. Ala92 type 2 deiodinase allele increases risk for the development of hypertension. Hypertension 2007, 49: 461-6.
124. Grarup N, Andersen MK, Andreasen CH, et al. Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects. J Clin Endocrinol Metab 2007, 92: 363-6. (Pubitemid 46067554)
125. Mentuccia D, Proietti-Pannunzi L, Tanner K, et al. Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. Diabetes 2002, 51:880-3. (Pubitemid 34760206)
126. Maia AL, Dupuis J, Manning A, et al. The type 2 deiodinase (DIO2) A/G polymorphism is not associated with glycemic traits: the Framingham Heart Study. Thyroid 2007, 17: 199-202. (Pubitemid 46557366)
127. Dora JM, Machado WE, Rheinheimer J, Crispim D, Maia AL. Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis. Eur J Endocrinol 163: 427-34.
128. Fiorito M, Torrente I, De Cosmo S, et al. Interaction of DIO2 T92A and PPARgamma2 P12A polymorphisms in the modulation of metabolic syndrome. Obesity (Silver Spring) 2007, 15: 2889-95. (Pubitemid 351256647)
129. Meulenbelt I, Min JL, Bos S, et al. Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis. Hum Mol Genet 2008, 17: 1867-5.
130. Peeters RP, van Toor H, Klootwijk W, et al. Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab 2003, 88: 2880-8. (Pubitemid 36724470)
131. Butler PW, Smith SM, Linderman JD, et al. The Thr92Ala 5′ type 2 deiodinase gene polymorphism is associated with a delayed triiodothyronine secretion in response to the thyrotropin-releasing hormone-stimulation test: a pharmacogenomic study. Thyroid 2010, 20: 1407-12.
132. Appelhof BC, Peeters RP, Wiersinga WM, et al. Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3′-triiodothyronine therapy. J Clin Endocrinol Metab 2005, 90: 6296-9. (Pubitemid 41606559)
133. Panicker V, Saravanan P, Vaidya B, et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J Clin Endocrinol Metab 2009, 94: 1623-9.
134. Meulenbelt I, Bos SD, Chapman K, et al; Translation Research in Europe Applied Technologies for Osteoarthritis (TreatOA). Meta-analyses of genes modulating intracellular T3 bio-availability reveal a possible role for the DIO3 gene in osteoarthritis susceptibility. Ann Rheum Dis 2011, 70: 164-7.