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The Selenoenzyme Family of Deiodinase Isozymes Controls Local Thyroid Hormone Availability

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References

  1. Köhrle J. The deiodinase family—selenoenzymes regulating thyroid hormone availability and action. Cellular Mol Life Sciences 1999; in press.

  2. Köhrle J. Local activation and inactivation of thyroid hormones: the deiodinase family. Mol Cell Endocrinol 1999;151:103–119.

    Google Scholar 

  3. Jakobs TC, Koehler MR, Schmutzler C, Glaser F, Schmid M, Köhrle J. Structure of the human type I iodothyronine 50-deiodinase gene and localization to chromosome 1p32-p33. Genomics 1997;42:361–363.

    Google Scholar 

  4. Maia AL, Berry MJ, Sabbag R, Harney JW, Larsen PR. Structural and functional differences in the dio 1 gene in mice with inherited type 1 deiodinase deficiency. Mol Endocrinol 1995; 9:969–980.

    Google Scholar 

  5. Leonard JL, KoÈhrle J. Intracellular pathways of thyroid hormone metabolism. In: Braverman LE, Utiger RD, (eds): Werner and Ingbar's The ThyroidÐA Fundamental and Clinical Text. Phildalphia, J.B. Lippincott Company, 2000: in press.

    Google Scholar 

  6. 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;15:5100–5112.

    Google Scholar 

  7. Jakobs T, Schmutzler C, Meissner J, KoÈhrle J. The promoter of the human type I 50-deiodinase gene: mapping of the transcription start site and identi®cation of a DR.4 thyroid hormone responsive element. Eur J Biochem 1997;247:288–297.

    Google Scholar 

  8. Schreck R, Schnieders F, Schmutzler C, KoÈhrle J. Retinoids stimulate Type I iodothyronine 50-deiodinase activity in human follicular thyroid carcinoma cell lines. J Clin Endocrinol Metab 1994;79:791–798.

    Google Scholar 

  9. KoÈhrle J. Thyroid carcinoma: interrelationships between local thyroid hormone metabolism by the type I 50-deiodinase and the expression of thyroid hormone receptors and other thyroid-specific (de-)differentiation markers. Curr Top Pathol 1997;91:83–116.

    Google Scholar 

  10. Miyashita K, Murakami M, Iriuchijiama T, Takeuchi T, Mori M. Regulation of rat liver type 1 iodothyronine deiodinase mRNA levels by testosterone. Mol Cell Endocrinol 1995;115:161–167.

    Google Scholar 

  11. Ogawa Y, Nishikawa M, Toyoda N, Yonemoto T, Gondou A, Inada M. Age and sex-related changes in type 1 iodothyronine deiodinase messenger ribonucleic acid in rat liver and kidney. Horm Metab Res 1999;31:295–299.

    Google Scholar 

  12. KoÈhrle J, Schomburg L, Drescher S, Fekete E, Bauer K. Rapid stimulation of type I 50-deiodinase in rat pituitaries by 3,30,5-triiodo-L-thyronine. Mol Cell Endocrinol 1995;108:17–21.

    Google Scholar 

  13. Rubio A, Menendez Pelaez A, Buzzell GR, Vaughan MK, Vaughan GM, Reiter RJ. Sexual differences in 50-deiodinase activity in the Harderian gland of Syrian hamsters and the effect of pinealectomy: regulation by androgens. J Cell Biochem 1996;62:397–404.

    Google Scholar 

  14. Kaplan MM, Utiger RD. Iodothyronine metabolism in rat liver homogenates. J Clin Invest 1978;61:459–471.

    Google Scholar 

  15. 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 50-deiodinase in rat primary hepatocyte cultures grown as spheroids. Endocrinology 1993;133:2984–2990.

    Google Scholar 

  16. Davies PH, Sheppard MC, Franklyn JA. Regulation of type I 50-deiodinase by thyroid hormone and dexamethasone in rat liver and kidney cells. Thyroid 1996;6:221–228.

    Google Scholar 

  17. Maia AL, Harney JW, Larsen PR. Pituitary cells respond to thyroid hormone by discrete, gene-specific pathways. Endocrinology 1995;136:1488–1494.

    Google Scholar 

  18. Hussain MA, Schmitz O, Jorgensen JO, Christiansen JS, Weeke J, Schmid C, Froesch ER. Insulin-like growth factor I alters peripheral thyroid hormone metabolism in humans: comparison with growth hormone. Eur J Endocrinol 1996;134:563–567.

    Google Scholar 

  19. Rose SR, Leong GM, Yanovski JA, Blum D, Heavner G, Barnes KM, Chipman JJ, Dichek HL, Jacobsen J, Klein KE, et al. Thyroid function in non-growth hormone-deficient short children during a placebo-controlled double blind trial of recombinant growth hormone therapy. J Clin Endocrinol Metab 1995;80:320–324.

    Google Scholar 

  20. Wyatt DT, Gesundheit N, Sherman B. Changes in thyroid hormone levels during growth hormone therapy in initially euthyroid patients: lack of need for thyroxine supplementation. J Clin Endocrinol Metab 1998;83:3493–3497.

    Google Scholar 

  21. Sato K, Robbins J. Thyroid Hormone Metabolism in Primary Cultured Rat Hepatocytes: Effect of Glucose, Glucagon, and Insulin. J Clin Invest 1981;68:475.

    Google Scholar 

  22. Harris ARC, Fang S-L, Vagenakis AG, Braverman LE. Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat. Metabolism 1978;27:1680–1690.

    Google Scholar 

  23. MuÈller MJ, KoÈhrle J, Hesch RD, Seitz HJ. Effect of cycloAMP on iodothyronine metabolism in the isolated perfused rat liver. Biochem Int 1982;5:495–501.

    Google Scholar 

  24. Gavin LA, Moeller M. The mechanism of recovery of hepatic T4–50-deiodinase during glucose-refeeding: Role of glucagon and insulin. Metabolism 1983;32:543–551.

    Google Scholar 

  25. Safran M, KoÈhrle J, Braverman LE, Leonard JL. Effect of biological alterations of type I 50deiodinase activity on af®nity labeled membrane proteins in rat liver and kidney. Endocrinology 1990;126:826–831.

    Google Scholar 

  26. O'Mara B, Dittrich W, Lauterio TJ, St.Germain DL. Pretranslational regulation of type I 50-deiodinase by thyroid hormones and in fasted and diabetic rats. Endocrinology 1994;133:1715–1723.

    Google Scholar 

  27. Rone JK, Dons RF, Reed HL. The effect of endurance training on serum triiodothyronine kinetics in man: physical conditioning marked by enhanced thyroid hormone metabolism. Clin Endocrinol (Oxf ) 1992;37:325–330.

    Google Scholar 

  28. Van Do N, LeMar H, Reed HL. Thyroid hormone responses to environmental cold exposure and seasonal changes: a proposed model. Endocrinology and Metabolism 1996;3:7–16.

    Google Scholar 

  29. Pilo A, Iervasi G, Vitek F, Ferdeghini M, Cazzuola F, Bianchi R. Thyroidal and peripheral production of 3,5,30-triiodothyronine in humans by multicompartmental analysis. American Journal of Physiology: Endocrinology and Metabolism 1990;258:E715-E726.

    Google Scholar 

  30. Pilo A, Iervasi G, Vitek F, Turchi S, Bianchi R. Disposal and distribution of rT3 in humans: a new double-tracer kinetic study. Am J Physiol 1993;264:E239-E249.

    Google Scholar 

  31. Nguyen TT, Chapa F, DiStefano JJ, III. Direct measurement of the contributions of type I and type II 50-deiodinases to whole body steady state 3,5,30-triiodothyronine production from thyroxine in the rat. Endocrinology 1998;139:4626–4633.

    Google Scholar 

  32. van Doorn J, Roelfsema F, Van der Heide D. Concentrations of thyroxine and 3,5,30-triiodothyronine at 34 different sites in euthyroid rats as determined by an isotopic equilibrium technique. Endocrinology 1985;117:1201–1208.

    Google Scholar 

  33. SchroÈder-Van der Elst JP, Van der Heide D, Morreale de Escobar G, ObregoÂn MJ. Iodothyronine deiodinase activities in fetal rat tissues at several levels of iodine de®ciency: A role for the skin in 3,5,30-triiodothyronine economy? Endocrinology 1998;139:2229–2234.

    Google Scholar 

  34. Arem R, Wiener GJ, Kaplan SG, Kim HS, Reichlin S, Kaplan MM. Reduced tissue thyroid hormone levels in fatal illness. Metabolism 1993;42:1102–1108.

    Google Scholar 

  35. De Groot LJ. Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J Clin Endocrinol Metab 1999;84:151–164.

    Google Scholar 

  36. Bartalena L, Bogazzi F, Brogioni S, Grasso L, Martino E. Role of cytokines in the pathogenesis of the euthyroid sick syndrome. Eur J Endocrinol 1998;138:603–614.

    Google Scholar 

  37. Chopra IJ. Simultaneous measurement of free thyroxine and free 3,5,30-triiodothyronine in undiluted serum by direct equilibrium dialysis/radioimmunoassay: evidence that free triiodothyronine and free thyroxine are normal in many patients with low triiodothyronine syndrome. Thyroid 1998;8:249–257.

    Google Scholar 

  38. Chopra IJ. Euthyroid sick Syndrome. Is it a misnomer? J Clin Endocrinol Metab 1997;82:329–334.

    Google Scholar 

  39. Van den Berghe G, Wouters P, Weekers F, Mohan S, Baxter RC, Veldhuis JD, Bowers CY, Bouillon R. Reactivation of pituitary 56 KoÈhrle hormone release and metabolic improvement by infusion of growth hormone-releasing peptide and thyrotropin-releasing hormone in patients with protracted critical illness. J Clin Endocrinol Metab 1999;84:1311–1323.

    Google Scholar 

  40. van der Poll T, van Zee KJ, Endert E, Coyle SM, Stiles DM, Pribble JP, Catalano MA, Moldawer LL, Lowry SF. Interleukin-1 receptor blockade does not affect endotoxin-induced changes in plasma thyroid hormone and thyrotropin concentrations in man. J Clin Endocrinol Metab 1995;80:1341–1346.

    Google Scholar 

  41. Torpy DJ, Tsigos C, Lotsikas AJ, Defensor R, Chrousos GP, Papanicolaou DA. Acute and delayed effects of a single-dose injection of interleukin-6 on thyroid function in healthy humans. Metabolism 1998;47:1289–1293.

    Google Scholar 

  42. Stouthard JM, van der Poll T, Endert E, Bakker PJ, Veenhof CH, Sauerwein HP, Romijn JA. Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans. J Clin Endocrinol Metab 1994;79:1342–1346.

    Google Scholar 

  43. Boelen A, Maas MAW, Lowik CWGM, Platvoet MC, Wiersinga WM. Induced illness in interleukin-6 (IL-6) knock-out mice: Causal role of IL-6 in the development of the low 3,5, 31-triiodothyronine syndrome. Endocrinology 1996;137:5250–5254.

    Google Scholar 

  44. Schmutzler C, Jakobs TC, Dreher I, Glaser F, KoÈhrle J. Regulation of type I 50-deiodinase (50DI) by proinflammatory cytokines in the human hepatocarcinoma cell line HepG2. J Endocrinol Invest 1998;21:2–2.

    Google Scholar 

  45. Köhrle J. Thyroid hormone metabolism and action in the brain and pituitary. Acta Med Austriaca 1999; in press.

  46. St.Germain DL, Galton VA. The Deiodinase Family of Selenoproteins. Thyroid 1997;7:655–668.

    Google Scholar 

  47. Celi FS, Canettieri G, Yarnall DP, Burns DK, Andreoli M, Shuldiner AR, Centanni M. Genomic characterization of the coding region of the human type II 50-deiodinase gene. Mol Cell Endocrinol 1998;14:49–52.

    Google Scholar 

  48. Köhrle J. The trace element selenium and the thyroid gland. Biochimie 1999;527–533.

  49. Davey JC, Schneider MJ, Becker KB, Galton VA. Cloning of a 5.8 kB cDNA for a mouse type 2 deiodinase. Endocrinology 1999;140:1022–1025.

    Google Scholar 

  50. Gereben B, Bartha T, Tu HM, Harney JW, Rudas P, Larsen PR. Cloning and expression of the chicken type 2 iodothyronine 50-deiodinase. J Biol Chem 1999;274:13768–13776.

    Google Scholar 

  51. Leonard JL, Leonard DM, Safran M, Wu R, Zapp ML, Farwell AP. The mammalian homolog of the frog type II selenodeiodinase does not encode a functional enzyme in the rat. Endocrinology 1999;140:2206–2215.

    Google Scholar 

  52. Safran M, Farwell AP, Leonard JL. Catalytic activity of type II iodothyronine 50-deiodinase polypeptide is dependent upon a cyclic AMP activation factor. J Biol Chem 1996;271:16363–16368.

    Google Scholar 

  53. Leonard JL, Farwell AP. Thyroid hormone-regulated actin polymerization in brain. Thyroid 1997;7:147–151.

    Google Scholar 

  54. Stulp MR, De Vijlder JJM, Ris-Stalpers C. Placental iodothyronine deiodinase III and II ratios, mRNA expression compared to enzyme activity. Mol Cell Endocrinol 1998;142:67–73.

    Google Scholar 

  55. Kim SW, Harney JW, Larsen PR. Studies of the hormonal regulation of type 2 50-iodothyronine deiodinase messenger ribonucleic acid in pituitary tumor cells using semiquantitative reverse transcription polymerase reaction. Endocrinology 1998;139:4895–4905.

    Google Scholar 

  56. Silva JE. Thyroid hormone control of thermogenesis and energy balance. Thyroid 1995;5:481–492.

    Google Scholar 

  57. Escobar-Morreale HF, ObregoÂn MJ, Escobar del Rey F, Morreale de Escobar G. Tissue-specific patterns of changes in 3,5,30-triiodo-Lthyronine concentrations in thyroidectomized rats infused with increasing doses of the hormone. Which are the regulatory mechanisms? Biochimie 1999;81:453–462.

    Google Scholar 

  58. Campos-Barros A, Musa A, Flechner A, Hessenius C, Gaio U, Meinold H, Baumgartner A. Evidence for circadian variations of thyroid hormone concentrations and type II 50-iodothyronine deiodinase acticity in the rat central nervous system. J Neurochem 1997;68:795–803.

    Google Scholar 

  59. Baumgartner A, Pinna G, Hiedra L, Gaio U, Hessenius C, Campos Barros A, Eravci M, Prengel H, Thoma R, Meinhold H. Effects of lithium and carbamazepine on thyroid hormone metabolism in rat brain. Neuropsychopharmacology 1997;16:25–41.

    Google Scholar 

  60. Campos-Barros A, Hoell T, Musa A, Sampaolo S, Stoltenburg G, Pinna G, Eravci M, Meinhold H, Baumgartner A. Phenolic and tyrosyl ring deiodination and thyroid hormone concentrations in the human central nervous system. J Clin Endocrinol Metab 1996;81:2179–2185.

    Google Scholar 

  61. Pavelka S, Kopecky P, Bendlova B, Stolba P, Vitkova I, Vobruba V, Plavka R, Houstek J, Kopecky J. Tissue metabolism and plasma levels of thyroid hormones in critically ill very premature infants. Pediatr Res 1997;42:812–818.

    Google Scholar 

  62. Calvo RM, Roda JM, Obregon MJ, Morreale de Escobar G. Thyroid hormones in human tumoral and normal nervous tissues. Brain Research 1998;801:150–157.

    Google Scholar 

  63. Guadano-Ferraz A, Bernal J. Regional expression of 50-deiodinase II in the rat brain as studied by in situ hybridization. Proc Natl Acad Sci USA 1997;94:10391–10396.

    Google Scholar 

  64. Tu HM, Kim S-W, Salvatore D, Bartha T, Legradi B, Larsen PR, Lechan RM. Regional distribution of type 2 thyroxine deiodinase messenger ribonucleic acid in rat hypothylamus and pituitary and its regulation by thyroid hormone. Endocrinology 1997;138:3359–3368.

    Google Scholar 

  65. Diano S, Naftolin F, Goglia F, Csernus V, Horvath TL. Monosynaptic pathway between the arcuate nucleus expressing glial type II iodothyronine 50-deiodinase mRNA and the median eminence-projective TRH cells of the rat paraventricular nucleus. J Neuroendocrinol 1998;10:731–742.

    Google Scholar 

  66. Guadano-Ferraz A, Escamez MJ, Rausell E, Bernal J. Expression of type 2 iodothyronine deiodinase in hypothyroid rat brain indicates an important role of thyroid hormone in the development of specific primary sensory systems. J Neurosci 1999;19:3430–3439.

    Google Scholar 

  67. Huang H, Marsh-Armstrong N, Brown DD. Metamorphosis is inbitied in transgenic Xenopus laevis tadpoles that overexpress type III deiodinase. Proc Natl Acad Sci USA 1999;96:962–967.

    Google Scholar 

  68. 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;103:979–987.

    Google Scholar 

  69. Tu HM, Legradi G, Bartha T, Salvatore D, Lechan RM, Larsen PR. Regional expression of the type 3 iodothyronine deiodinase messenger ribonucleic acid in the rat central nervous system and its regulation by thyroid hormone. Endocrinology 1999;140:784–790.

    Google Scholar 

  70. Bates JM, St. Germain DL, Galton VA. Expression pro®les of three iodothyronine deiodinases D1, D2, D3, in the developing rat. Endocrinology 1999;140:844–851.

    Google Scholar 

  71. Salvatore D, Low SC, Berry M, Maia AL, Harney JW, Croteau W, St. Germain DL, Larsen PR. Type 3 iodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme. J Clin Invest 1995;96:2421–2430.

    Google Scholar 

  72. Koopdonk Kool JM, De Vijlder JJ, Veenboer GJ, Ris Stalpers C, Kok JH, Vulsma T, Boer K, Visser TJ. Type II and type III deiodinase activity in human placenta as a function of gestational age. J Clin Endocrinol Metab 1996;81:2154–2158.

    Google Scholar 

  73. Santini F, Chiovato L, Ghirri P, Lapi P, Mammoli C, Montanellli L, Scartabelli G, Ceccarini G, Coccoli L, Chopra IJ, Boldrini A, Pinchera A. 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;84:493–498.

    Google Scholar 

  74. Krysin E, Brzezinska-Slebodinska E, Slebodzinski AB. Divergent deiodination of thyroid hormones in the separated parts of fetal and maternal placenta in pigs. J Endocrinol 1997;155:295–303.

    Google Scholar 

  75. HernaÂndez A, St. Germain DL, Obregon MJ. Transcriptional activation of type III inner ring deiodinase by growth factors in cultured rat brown adipocytes. Endocrinology 1998;139:634–639.

    Google Scholar 

  76. Baur A, Bauer K, Jarry H, KoÈhrle J. 3,5-Di-iodo-L-thyronine stimulates type I 50-deiodinase activity in rat anterior pituitaries in vivo and in reaggregate cultures and GH3 cells in vitro. Endocrinology 1997;138:3242–3248.

    Google Scholar 

  77. Baur A, KoÈhrle J. Type I 50-deiodinase is stimulated by iodothyronines and involved in thyroid hormone metabolism in human somatomammotroph GX cells. Eur J Endocrinol 1999;367–370.

  78. Richard K, Hume R, Kaptein E, Sanders JP, Van Toor H, De Herder WW, den Hollander JC, Krenning E, Visser TJ. Ontogeny of iodothyronine deiodinases in human liver. J Clin Endocrinol Metab 1998;83:2868–2874.

    Google Scholar 

  79. HernaÂndez A, Park JP, Lyon GJ, Mohandas TK, St. Germain DL. Localization of the type 3 iodothyronine deiodinase (DIO3) gene to human chromosome 14q32 and mouse chromosome 12F1. Genomics 1998;53:119–121.

    Google Scholar 

  80. HernaÂndez A, Lyon GJ, Schneider MJ, St. Germain DL. Isolation and characterization of the mouse gene for the type 3 iodothyronine deiodinase. Endocrinology 1999;140:124–130.

    Google Scholar 

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Ko¨hrle, J. The Selenoenzyme Family of Deiodinase Isozymes Controls Local Thyroid Hormone Availability. Rev Endocr Metab Disord 1, 49–58 (2000). https://doi.org/10.1023/A:1010012419869

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