Advertisement

Deiodination and Peripheral Metabolism of Thyroid Hormone

  • Monica DenticeEmail author
  • Domenico Salvatore
Chapter

Abstract

Canonical thyroid hormone (TH) signaling results from the interaction of T3 with nuclear receptors and stimulation or repression target genes. Ligand (T3) availability is under tight control of several intracellular checkpoints, which enable target cells to modify their own T3 fingerprint. A crucial step of intracellular T3 metabolism is catalyzed by the deiodinases. These enzymes can, within the single cell, enhance (D1 and D2) or reduce (D3) T3 concentrations. Thyroid hormone transport within the target cells is also a limiting step of thyroid hormone action. Various specific transporters have been isolated for the entrance and the clearance of the iodothyronines and constitute a complex system of active transport of THs inside and outside the cells. Concerted modulation of the different TH regulating factors is responsible for a spatiotemporal precise adaptation of the hormonal signal to the different cell-specific requirements.

Keywords

Thyroid hormone Deiodinases Nuclear receptors 

References

  1. 1.
    Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeold A, Bianco AC. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008;29:898–938.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Crantz FR, Silva JE, Larsen PR. An analysis of the sources and quantity of 3,5,3′-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology. 1982;110:367–75.PubMedCrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    St Germain DL, Galton VA. The deiodinase family of selenoproteins. Thyroid. 1997;7:655–68.PubMedCrossRefGoogle Scholar
  5. 5.
    Oppenheimer JH, Schwartz HL, Surks MI. Propylthiouracil inhibits the conversion of L-thyroxine to L-triiodothyronine. An explanation of the antithyroxine effect of propylthiouracil and evidence supporting the concept that triiodothyronine is the active thyroid hormone. J Clin Invest. 1972;51:2493–7.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Leonard JL, Rosenberg IN. Thyroxine 5′-deiodinase activity of rat kidney: observations on activation by thiols and inhibition by propylthiouracil. Endocrinology. 1978;103:2137–44.PubMedCrossRefGoogle Scholar
  7. 7.
    Maia AL, Berry MJ, Sabbag R, Harney JW, Larsen PR. Structural and functional differences in the dio1 gene in mice with inherited type 1 deiodinase deficiency. Mol Endocrinol. 1995;9:969–80.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Curcio-Morelli C, Gereben B, Zavacki AM, Kim BW, Huang S, Harney JW, Larsen PR, Bianco AC. In vivo dimerization of types 1, 2, and 3 iodothyronine selenodeiodinases. Endocrinology. 2003;144:937–46.PubMedCrossRefGoogle Scholar
  9. 9.
    Visser TJ, van den Hout-Goemaat NL, Docter R, Hennemann G. Radio-immunoassay of thyroxine in unextracted serum. Neth J Med. 1975;18:111–5.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Chopra IJ. A study of extrathyroidal conversion of thyroxine (T4) to 3,3′,5-triiodothyronine (T3) in vitro. Endocrinology. 1977;101:453–63.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Kaplan MM, Utiger RD. Iodothyronine metabolism in rat liver homogenates. J Clin Invest. 1978;61:459–71.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    O'Mara BA, Dittrich W, Lauterio TJ, St Germain DL. Pretranslational regulation of type I 5′-deiodinase by thyroid hormones and in fasted and diabetic rats. Endocrinology. 1993;133:1715–23.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Debaveye Y, Ellger B, Mebis L, Darras VM, Van den Berghe G. Regulation of tissue iodothyronine deiodinase activity in a model of prolonged critical illness. Thyroid. 2008;18:551–60.PubMedCrossRefGoogle Scholar
  14. 14.
    Chopra IJ. Clinical review 86: Euthyroid sick syndrome: is it a misnomer? J Clin Endocrinol Metab. 1997;82:329–34.PubMedCrossRefGoogle Scholar
  15. 15.
    Peeters RP, van der Geyten S, Wouters PJ, Darras VM, van Toor H, Kaptein E, Visser TJ, Van den Berghe G. Tissue thyroid hormone levels in critical illness. J Clin Endocrinol Metab. 2005;90:6498–507.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Schneider MJ, Fiering SN, Thai B, Wu SY, St Germain E, Parlow AF, St Germain DL, Galton VA. Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology. 2006;147:580–9.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Larsen PR, Silva JE, Kaplan MM. Relationships between circulating and intracellular thyroid hormones: physiological and clinical implications. Endocr Rev. 1981;2:87–102.PubMedCrossRefGoogle Scholar
  18. 18.
    Buettner C, Harney JW, Larsen PR. The 3′-untranslated region of human type 2 iodothyronine deiodinase mRNA contains a functional selenocysteine insertion sequence element. J Biol Chem. 1998;273:33374–8.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Croteau W, Davey JC, Galton VA, St Germain DL. Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. J Clin Invest. 1996;98:405–17.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    de Jesus LA, Carvalho SD, Ribeiro MO, Schneider M, Kim SW, Harney JW, Larsen PR, Bianco AC. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest. 2001;108:1379–85.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Salvatore D, Bartha T, Harney JW, Larsen PR. Molecular biological and biochemical characterization of the human type 2 selenodeiodinase. Endocrinology. 1996;137:3308–15.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Dentice M, Marsili A, Ambrosio R, Guardiola O, Sibilio A, Paik JH, Minchiotti G, DePinho RA, Fenzi G, Larsen PR, et al. The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. J Clin Invest. 2010;120:4021–30.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Salvatore D, Simonides WS, Dentice M, Zavacki AM, Larsen PR. Thyroid hormones and skeletal muscle--new insights and potential implications. Nat Rev Endocrinol. 2014;10:206–14.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Ramadan W, Marsili A, Larsen PR, Zavacki AM, Silva JE. Type-2 iodothyronine 5’deiodinase (D2) in skeletal muscle of C57Bl/6 mice. II. Evidence for a role of D2 in the hypermetabolism of thyroid hormone receptor alpha-deficient mice. Endocrinology. 2011;152:3093–102.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Marsili A, Ramadan W, Harney JW, Mulcahey M, Castroneves LA, Goemann IM, Wajner SM, Huang SA, Zavacki AM, Maia AL, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Dentice M, Salvatore D. Deiodinases: the balance of thyroid hormone: local impact of thyroid hormone inactivation. J Endocrinol. 2011;209:273–82.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Salvatore D, Low SC, Berry M, Maia AL, Harney JW, Croteau W, St Germain DL, Larsen PR. Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme. J Clin Invest. 1995;96:2421–30.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Marsh-Armstrong N, Huang H, Remo BF, Liu TT, Brown DD. Asymmetric growth and development of the Xenopus laevis retina during metamorphosis is controlled by type III deiodinase. Neuron. 1999;24:871–8.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Kester MH, Toussaint MJ, Punt CA, Matondo R, Aarnio AM, Darras VM, Everts ME, de Bruin A, Visser TJ. Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver. Endocrinology. 2009;150:540–5.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Dentice M, Ambrosio R, Damiano V, Sibilio A, Luongo C, Guardiola O, Yennek S, Zordan P, Minchiotti G, Colao A, et al. Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression. Cell Metab. 2014;20:1038–48.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Li WW, Le Goascogne C, Ramauge M, Schumacher M, Pierre M, Courtin F. Induction of type 3 iodothyronine deiodinase by nerve injury in the rat peripheral nervous system. Endocrinology. 2001;142:5190–7.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Boelen A, Kwakkel J, Alkemade A, Renckens R, Kaptein E, Kuiper G, Wiersinga WM, Visser TJ. Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation. Endocrinology. 2005;146:5128–34.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Dentice M, Luongo C, Huang S, Ambrosio R, Elefante A, Mirebeau-Prunier D, Zavacki AM, Fenzi G, Grachtchouk M, Hutchin M, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Dentice M, Luongo C, Ambrosio R, Sibilio A, Casillo A, Iaccarino A, Troncone G, Fenzi G, Larsen PR, Salvatore D. beta-catenin regulates deiodinase levels and thyroid hormone signaling in colon cancer cells. Gastroenterology. 2012;143:1037–47.PubMedCrossRefGoogle Scholar
  35. 35.
    Huang SA, Tu HM, Harney JW, Venihaki M, Butte AJ, Kozakewich HP, Fishman SJ, Larsen PR. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med. 2000;343:185–9.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Huang SA, Fish SA, Dorfman DM, Salvatore D, Kozakewich HP, Mandel SJ, Larsen PR. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Di Girolamo D, Ambrosio R, De Stefano MA, Mancino G, Porcelli T, Luongo C, Di Cicco E, Scalia G, Vecchio LD, Colao A, et al. Reciprocal interplay between thyroid hormone and microRNA-21 regulates hedgehog pathway-driven skin tumorigenesis. J Clin Invest. 2016;126:2308–20.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, Wassen FW, Crescenzi A, da-Silva WS, Harney J, et al. Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats. J Clin Invest. 2008;118:975–83.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Wassen FW, Schiel AE, Kuiper GG, Kaptein E, Bakker O, Visser TJ, Simonides WS. Induction of thyroid hormone-degrading deiodinase in cardiac hypertrophy and failure. Endocrinology. 2002;143:2812–5.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Rajabi M, Kassiotis C, Razeghi P, Taegtmeyer H. Return to the fetal gene program protects the stressed heart: a strong hypothesis. Heart Fail Rev. 2007;12:331–43.PubMedCrossRefGoogle Scholar
  41. 41.
    Siegel E, Sachs BA. In vitro leukocyte uptake of 131-I labeled iodide, thyroxine and triiodothyronine, and its relation to thyroid function. J Clin Endocrinol Metab. 1964;24:313–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Boelen A, Kwakkel J, Vos XG, Wiersinga WM, Fliers E. Differential effects of leptin and refeeding on the fasting-induced decrease of pituitary type 2 deiodinase and thyroid hormone receptor beta2 mRNA expression in mice. J Endocrinol. 2006;190:537–44.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Boelen A, Wiersinga WM, Fliers E. Fasting-induced changes in the hypothalamus-pituitary-thyroid axis. Thyroid. 2008;18:123–9.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Boelen A, Kwakkel J, Wieland CW, St Germain DL, Fliers E, Hernandez A. Impaired bacterial clearance in type 3 deiodinase-deficient mice infected with Streptococcus pneumoniae. Endocrinology. 2009;150:1984–90.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Peeters RP, Wouters PJ, Kaptein E, van Toor H, Visser TJ, Van den Berghe G. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab. 2003;88:3202–11.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Rodriguez-Perez A, Palos-Paz F, Kaptein E, Visser TJ, Dominguez-Gerpe L, Alvarez-Escudero J, Lado-Abeal J. Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock. Clin Endocrinol. 2008;68:821–7.CrossRefGoogle Scholar
  47. 47.
    Peeters RP, Wouters PJ, van Toor H, Kaptein E, Visser TJ, Van den Berghe G. 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.PubMedCrossRefGoogle Scholar
  48. 48.
    Fausto N. Liver regeneration. J Hepatol. 2000;32:19–31.PubMedCrossRefGoogle Scholar
  49. 49.
    Tanimizu N, Miyajima A. Molecular mechanism of liver development and regeneration. Int Rev Cytol. 2007;259:1–48.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Hennemann G, Krenning EP, Polhuys M, Mol JA, Bernard BF, Visser TJ, Docter R. Carrier-mediated transport of thyroid hormone into rat hepatocytes is rate-limiting in total cellular uptake and metabolism. Endocrinology. 1986;119:1870–2.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem. 2003;278:40128–35.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Visser WE, Friesema EC, Jansen J, Visser TJ. Thyroid hormone transport in and out of cells. Trends Endocrinol Metab. 2008;19:50–6.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Hennemann G, Docter R, Friesema EC, de Jong M, Krenning EP, Visser TJ. Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr Rev. 2001;22:451–76.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, et al. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet. 2004;364:1435–7.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet. 2004;74:168–75.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Visser WE, Visser TJ. Finding the way into the brain without MCT8. J Clin Endocrinol Metab. 2012;97:4362–5.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ. Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8. Nat Clin Pract Endocrinol Metab. 2006;2:512–23.PubMedCrossRefGoogle Scholar
  58. 58.
    Visser WE, Friesema EC, Visser TJ. Minireview: thyroid hormone transporters: the knowns and the unknowns. Mol Endocrinol. 2011;25:1–14.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Wirth EK, Roth S, Blechschmidt C, Holter SM, Becker L, Racz I, Zimmer A, Klopstock T, Gailus-Durner V, Fuchs H, et al. Neuronal 3′,3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome. J Neurosci. 2009;29:9439–49.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Trajkovic M, Visser TJ, Mittag J, Horn S, Lukas J, Darras VM, Raivich G, Bauer K, Heuer H. Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8. J Clin Invest. 2007;117:627–35.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Dumitrescu AM, Liao XH, Weiss RE, Millen K, Refetoff S. Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice. Endocrinology. 2006;147:4036–43.PubMedCrossRefGoogle Scholar
  62. 62.
    Mayerl S, Visser TJ, Darras VM, Horn S, Heuer H. Impact of Oatp1c1 deficiency on thyroid hormone metabolism and action in the mouse brain. Endocrinology. 2012;153:1528–37.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Heuer H, Maier MK, Iden S, Mittag J, Friesema EC, Visser TJ, Bauer K. The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations. Endocrinology. 2005;146:1701–6.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Bernal J. Thyroid hormones and brain development. Vitam Horm. 2005;71:95–122.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Toyoda N, Zavacki AM, Maia AL, Harney JW, Larsen PR. A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene. Mol Cell Biol. 1995;15:5100–12.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Jakobs TC, Schmutzler C, Meissner J, Kohrle J. The promoter of the human type I 5′-deiodinase gene--mapping of the transcription start site and identification of a DR+4 thyroid-hormone-responsive element. Eur J Biochem. 1997;247:288–97.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Botero D, Gereben B, Goncalves C, De Jesus LA, Harney JW, Bianco AC. Ubc6p and ubc7p are required for normal and substrate-induced endoplasmic reticulum-associated degradation of the human selenoprotein type 2 iodothyronine monodeiodinase. Mol Endocrinol. 2002;16:1999–2007.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Esfandiari A, Gagelin C, Gavaret JM, Pavelka S, Lennon AM, Pierre M, Courtin F. Induction of type III-deiodinase activity in astroglial cells by retinoids. Glia. 1994;11:255–61.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Alcantara MR, Salvatori R, Alcantara PR, Nobrega LM, Campos VS, Oliveira EC, Oliveira MH, Souza AH, Aguiar-Oliveira MH. Thyroid morphology and function in adults with untreated isolated growth hormone deficiency. J Clin Endocrinol Metab. 2006;91:860–4.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Pekary AE, Berg L, Santini F, Chopra I, Hershman JM. Cytokines modulate type I iodothyronine deiodinase mRNA levels and enzyme activity in FRTL-5 rat thyroid cells. Mol Cell Endocrinol. 1994;101:R31–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Menjo M, Murata Y, Fujii T, Nimura Y, Seo H. Effects of thyroid and glucocorticoid hormones on the level of messenger ribonucleic acid for iodothyronine type I 5′-deiodinase in rat primary hepatocyte cultures grown as spheroids. Endocrinology. 1993;133:2984–90.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Van der Geyten S, Darras VM. Developmentally defined regulation of thyroid hormone metabolism by glucocorticoids in the rat. J Endocrinol. 2005;185:327–36.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Canettieri G, Franchi A, Sibilla R, Guzman E, Centanni M. Functional characterisation of the CRE/TATA box unit of type 2 deiodinase gene promoter in a human choriocarcinoma cell line. J Mol Endocrinol. 2004;33:51–8.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Gereben B, Salvatore D, Harney JW, Tu HM, Larsen PR. The human, but not rat, dio2 gene is stimulated by thyroid transcription factor-1 (TTF-1). Mol Endocrinol. 2001;15:112–24.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Dentice M, Morisco C, Vitale M, Rossi G, Fenzi G, Salvatore D. The different cardiac expression of the type 2 iodothyronine deiodinase gene between human and rat is related to the differential response of the Dio2 genes to Nkx-2.5 and GATA-4 transcription factors. Mol Endocrinol. 2003;17:1508–21.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Zeold A, Doleschall M, Haffner MC, Capelo LP, Menyhert J, Liposits Z, da Silva WS, Bianco AC, Kacskovics I, Fekete C, et al. Characterization of the nuclear factor-kappa B responsiveness of the human dio2 gene. Endocrinology. 2006;147:4419–29.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Dentice M, Luongo C, Elefante A, Ambrosio R, Salzano S, Zannini M, Nitsch R, Di Lauro R, Rossi G, Fenzi G, et al. Pendrin is a novel in vivo downstream target gene of the TTF-1/Nkx-2.1 homeodomain transcription factor in differentiated thyroid cells. Mol Cell Biol. 2005;25:10171–82.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Dentice M, Bandyopadhyay A, Gereben B, Callebaut I, Christoffolete MA, Kim BW, Nissim S, Mornon JP, Zavacki AM, Zeold A, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Curcio-Morelli C, Zavacki AM, Christofollete M, Gereben B, de Freitas BC, Harney JW, Li Z, Wu G, Bianco AC. Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation. J Clin Invest. 2003;112:189–96.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15:3059–87.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Gereben B, Zeold A, Dentice M, Salvatore D, Bianco AC. Activation and inactivation of thyroid hormone by deiodinases: local action with general consequences. Cell Mol Life Sci. 2008;65:570–90.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Huang SA, Mulcahey MA, Crescenzi A, Chung M, Kim BW, Barnes C, Kuijt W, Turano H, Harney J, Larsen PR. Transforming growth factor-beta promotes inactivation of extracellular thyroid hormones via transcriptional stimulation of type 3 iodothyronine deiodinase. Mol Endocrinol. 2005;19:3126–36.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    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.PubMedCrossRefGoogle Scholar
  86. 86.
    Ng L, Goodyear RJ, Woods CA, Schneider MJ, Diamond E, Richardson GP, Kelley MW, Germain DL, Galton VA, Forrest D. Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase. Proc Natl Acad Sci U S A. 2004;101:3474–9.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Dussault JH, Coulombe P, Walker P. Effects of neonatal hyperthyroidism on the development of the hypothalamic-pituitary-thyroid axis in the rat. Endocrinology. 1982;110:1037–42.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Medicine and SurgeryUniversity of Naples “Federico II”NaplesItaly

Personalised recommendations