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“Thyroglobulin Storage, Processing and Degradation for Thyroid Hormone Liberation”

  • Klaudia BrixEmail author
  • Maria Qatato
  • Joanna Szumska
  • Vaishnavi Venugopalan
  • Maren Rehders
Chapter

Abstract

The tasks of the thyroid gland comprise (1) thyroid hormone (TH) generation via synthesis of the prohormone thyroglobulin (Tg), (2) import and organification of iodine resulting in the generation of preformed TH bound to Tg, (3) Tg storage in covalently cross-linked form in the extracellular follicle lumen, (4) TH demand-driven solubilization of Tg from its storage forms, (5) proteolytic processing of Tg for TH liberation by extra- and intracellular means, (6) complete degradation of Tg upon its re-internalization, and (7) TH release into the bloodstream. Therefore, this chapter focuses on thyroid cell biology and describes how classical thyroid hormones are generated, liberated, and released from thyroid follicles.

Keywords

Cathepsins Covalent cross-linkage Endocytosis Extracellular thyroglobulin processing Intracellular thyroglobulin degradation Lysosomes Proteases Protein processing Thyroglobulin Trafficking 

Abbreviations

AFU

Angio-follicular unit

CH

Congenital hyperthyroidism

CNS

Central nervous system

Cts

Cathepsin gene

DIT

Diiodothyronines

DUOX

Dual oxidase

ER

Endoplasmic reticulum

ERAD

ER-associated degradation

fT4

Free T4

IYD

Iodotyrosine deiodinase

M6P

Mannose 6-phosphate

MIT

Monoiodothyronines

MPR

Mannose 6-phosphate receptor

NIS

Sodium-iodide symporter

PDI

Protein disulfide isomerase

rER

Rough endoplasmic reticulum

rT3

Reverse T3

T2

3,3′-Diiodothyronine and 3,5-diiodothyronine

T3

3,5,3′-Triiodothyronine

T4

3,5,3′,5′-Tetraiodothyronine, thyroxine

TAM

Thyronamines

Tg

Thyroglobulin

TGN

trans-Golgi network

TH

Thyroid hormone

TPO

Thyroid peroxidase

TSH

Thyroid-stimulating hormone

References

  1. 1.
    Brix K, Führer D, Biebermann H. Molecules important for thyroid hormone synthesis and action—known facts and future perspectives. Thyroid Res. 2011;4(Suppl 1):S9.  https://doi.org/10.1186/1756-6614-4-s1-s9.PubMedCentralPubMedGoogle Scholar
  2. 2.
    Führer D, Brix K, Biebermann H. Thyroid hormone action beyond classical concepts. The priority programme “thyroid trans act” (SPP 1629) of the German Research Foundation. Dtsch Med Wochenschr. 2014;139(10):492–6.  https://doi.org/10.1055/s-0034-1369822.PubMedGoogle Scholar
  3. 3.
    Piehl S, Hoefig CS, Scanlan TS, Kohrle J. Thyronamines—past, present, and future. Endocr Rev. 2011;32(1):64–80.  https://doi.org/10.1210/er.2009-0040.PubMedGoogle Scholar
  4. 4.
    Bianco AC, Kim BW. Deiodinases: implications of the local control of thyroid hormone action. J Clin Investig. 2006;116(10):2571–9.  https://doi.org/10.1172/JCI29812.PubMedGoogle Scholar
  5. 5.
    Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev. 2010;31(2):139–70.  https://doi.org/10.1210/er.2009-0007.PubMedCentralPubMedGoogle Scholar
  6. 6.
    Dayan CM, Panicker V. Novel insights into thyroid hormones from the study of common genetic variation. Nat Rev Endocrinol. 2009;5(4):211–8.  https://doi.org/10.1038/nrendo.2009.19.PubMedGoogle Scholar
  7. 7.
    Kohrle J. Thyroid hormone transporters in health and disease: advances in thyroid hormone deiodination. Best Pract Res Clin Endocrinol Metab. 2007;21(2):173–91.  https://doi.org/10.1016/j.beem.2007.04.001.PubMedGoogle Scholar
  8. 8.
    Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014;94(2):355–82.  https://doi.org/10.1152/physrev.00030.2013.PubMedCentralPubMedGoogle Scholar
  9. 9.
    St Germain DL, Galton VA, Hernandez A. Minireview: defining the roles of the iodothyronine deiodinases: current concepts and challenges. Endocrinology. 2009;150(3):1097–107.  https://doi.org/10.1210/en.2008-1588.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Schweizer U, Chiu J, Kohrle J. Peroxides and peroxide-degrading enzymes in the thyroid. Antioxid Redox Signal. 2008;10(9):1577–92.  https://doi.org/10.1089/ars.2008.2054.PubMedGoogle Scholar
  11. 11.
    Fujita H. Functional morphology of the thyroid. In: Jeon KW, Friedlander M, editors. International review of cytology, vol. 113. London: Academic Press; 1988. p. 145–85.  https://doi.org/10.1016/S0074-7696(08)60848-7.Google Scholar
  12. 12.
    Nilsson M, Fagman H. Mechanisms of thyroid development and dysgenesis: an analysis based on developmental stages and concurrent embryonic anatomy. Curr Top Dev Biol. 2013;106:123–70.  https://doi.org/10.1016/b978-0-12-416021-7.00004-3.PubMedGoogle Scholar
  13. 13.
    Johansson E, Andersson L, Ornros J, Carlsson T, Ingeson-Carlsson C, Liang S, Dahlberg J, Jansson S, Parrillo L, Zoppoli P, Barila GO, Altschuler DL, Padula D, Lickert H, Fagman H, Nilsson M. Revising the embryonic origin of thyroid C cells in mice and humans. Development. 2015;142(20):3519–28.  https://doi.org/10.1242/dev.126581.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Nilsson M, Williams D. On the origin of cells and derivation of thyroid cancer: C cell story revisited. Eur Thyroid J. 2016;5(2):79–93.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Colin IM, Denef JF, Lengele B, Many MC, Gerard AC. Recent insights into the cell biology of thyroid angiofollicular units. Endocr Rev. 2013;34(2):209–38.  https://doi.org/10.1210/er.2012-1015.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Colin I, Gerard AC. The thyroid angiofollicular units, a biological model of functional and morphological integration. Bull Mem Acad R Med Belg. 2010;165(5–6):218–28; discussion 228-230.PubMedGoogle Scholar
  17. 17.
    Ohtani O, Ohtani Y. Organization and developmental aspects of lymphatic vessels. Arch Histol Cytol. 2008;71(1):1–22.PubMedGoogle Scholar
  18. 18.
    Malthiery Y, Lissitzky S. Sequence of the 5′-end quarter of the human-thyroglobulin messenger ribonucleic acid and of its deduced amino-acid sequence. Eur J Biochem. 1985;147(1):53–8.  https://doi.org/10.1111/j.1432-1033.1985.tb08717.x.PubMedGoogle Scholar
  19. 19.
    Mercken L, Simons MJ, Swillens S, Massaer M, Vassart G. Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA. Nature. 1985;316(6029):647–51.PubMedGoogle Scholar
  20. 20.
    van Herle AJ, Vassart G, Dumont JE. Control of thyroglobulin synthesis and secretion. (first of two parts). N Engl J Med. 1979;301(5):239–49.  https://doi.org/10.1056/nejm197908023010504.PubMedGoogle Scholar
  21. 21.
    Malthiery Y, Lissitzky S. Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA. Eur J Biochem. 1987;165(3):491–8.PubMedGoogle Scholar
  22. 22.
    Di Jeso B, Arvan P. Thyroglobulin from molecular and cellular biology to clinical endocrinology. Endocr Rev. 2016;37(1):2–36.  https://doi.org/10.1210/er.2015-1090.PubMedGoogle Scholar
  23. 23.
    Holzer G, Morishita Y, Fini JB, Lorin T, Gillet B, Hughes S, Tohme M, Deleage G, Demeneix B, Arvan P, Laudet V. Thyroglobulin represents a novel molecular architecture of vertebrates. J Biol Chem. 2016;291:16553–66.  https://doi.org/10.1074/jbc.M116.719047.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Desruisseau S, Franc JL, Gruffat D, Chabaud O. Glycosylation of thyroglobulin secreted by porcine cells cultured in chamber system: thyrotropin controls the number of oligosaccharides and their anionic residues. Endocrinology. 1994;134(4):1676–84.  https://doi.org/10.1210/endo.134.4.8137731.PubMedGoogle Scholar
  25. 25.
    Dunn J. Thyroglobulin: chemistry and biosynthesis. In: Braverman LE, Utiger RD, editors. The thyroid A fundamental and clinical text. Philadelphia, PA: Lippincott-Raven; 1996. p. 85–95.Google Scholar
  26. 26.
    Kornfeld R, Kornfeld S. Structure of glycoproteins and their oligosaccharide units. In: Lennarz WJ, editor. The biochemistry of glycoproteins and proteoglycans. Boston, MA: Springer US; 1980. p. 1–34.  https://doi.org/10.1007/978-1-4684-1006-8_1.Google Scholar
  27. 27.
    Rawitch AB, Pollock HG, Yang SX. Thyroglobulin glycosylation: location and nature of the N-linked oligosaccharide units in bovine thyroglobulin. Arch Biochem Biophys. 1993;300(1):271–9.  https://doi.org/10.1006/abbi.1993.1038.PubMedGoogle Scholar
  28. 28.
    Ring P, Bjorkman U, Johanson V, Ekholm R. The effect of monensin on thyroglobulin secretion. Studies with isolated follicles from pig thyroids. Cell Tissue Res. 1987;248(1):153–60.PubMedGoogle Scholar
  29. 29.
    Tsuji T, Yamamoto K, Irimura T, Osawa T. Structure of carbohydrate unit a or porcine thyroglobulin. Biochem J. 1981;195(3):691–9.PubMedCentralPubMedGoogle Scholar
  30. 30.
    van de Graaf SA, Ris-Stalpers C, Pauws E, Mendive FM, Targovnik HM, De Vijlder JJ. Up to date with human thyroglobulin. J Endocrinol. 2001;170(2):307–21.PubMedGoogle Scholar
  31. 31.
    Yang SX, Pollock HG, Rawitch AB. Glycosylation in human thyroglobulin: location of the N-linked oligosaccharide units and comparison with bovine thyroglobulin. Arch Biochem Biophys. 1996;327(1):61–70.  https://doi.org/10.1006/abbi.1996.0093.PubMedGoogle Scholar
  32. 32.
    Herzog V. Pathways of endocytosis in thyroid follicle cells. Int Rev Cytol. 1984;91:107–39.PubMedGoogle Scholar
  33. 33.
    Kim PS, Arvan P. Endocrinopathies in the family of endoplasmic reticulum (ER) storage diseases: disorders of protein trafficking and the role of ER molecular chaperones. Endocr Rev. 1998;19(2):173–202.  https://doi.org/10.1210/edrv.19.2.0327.PubMedGoogle Scholar
  34. 34.
    Venkatesh SG, Deshpande V. A comparative review of the structure and biosynthesis of thyroglobulin. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1999;122(1):13–20.PubMedGoogle Scholar
  35. 35.
    Grasberger H, Refetoff S. Genetic causes of congenital hypothyroidism due to dyshormonogenesis. Curr Opin Pediatr. 2011;23(4):421–8.  https://doi.org/10.1097/MOP.0b013e32834726a4.PubMedCentralPubMedGoogle Scholar
  36. 36.
    Park YN, Arvan P. The acetylcholinesterase homology region is essential for normal conformational maturation and secretion of thyroglobulin. J Biol Chem. 2004;279(17):17085–9.  https://doi.org/10.1074/jbc.M314042200.PubMedGoogle Scholar
  37. 37.
    Szinnai G. Genetics of normal and abnormal thyroid development in humans. Best Pract Res Clin Endocrinol Metab. 2014;28(2):133–50.  https://doi.org/10.1016/j.beem.2013.08.005.PubMedGoogle Scholar
  38. 38.
    Arvan P, Kim PS, Kuliawat R, Prabakaran D, Muresan Z, Yoo SE, Abu Hossain S. Intracellular protein transport to the thyrocyte plasma membrane: potential implications for thyroid physiology. Thyroid. 1997;7(1):89–105.  https://doi.org/10.1089/thy.1997.7.89.PubMedGoogle Scholar
  39. 39.
    Kim PS, Arvan P. Folding and assembly of newly synthesized thyroglobulin occurs in a pre-Golgi compartment. J Biol Chem. 1991;266(19):12412–8.PubMedGoogle Scholar
  40. 40.
    Rubio IG, Medeiros-Neto G. Mutations of the thyroglobulin gene and its relevance to thyroid disorders. Curr Opin Endocrinol Diabetes Obes. 2009;16(5):373–8.  https://doi.org/10.1097/MED.0b013e32832ff218.PubMedGoogle Scholar
  41. 41.
    Coutinho MF, Prata MJ, Alves S. Mannose-6-phosphate pathway: a review on its role in lysosomal function and dysfunction. Mol Genet Metab. 2012a;105(4):542–50.  https://doi.org/10.1016/j.ymgme.2011.12.012.PubMedGoogle Scholar
  42. 42.
    Coutinho MF, Prata MJ, Alves S. A shortcut to the lysosome: the mannose-6-phosphate-independent pathway. Mol Genet Metab. 2012b;107(3):257–66.  https://doi.org/10.1016/j.ymgme.2012.07.012.PubMedGoogle Scholar
  43. 43.
    De Duve C, Wattiaux R. Functions of lysosomes. Annu Rev Physiol. 1966;28:435–92.  https://doi.org/10.1146/annurev.ph.28.030166.002251.PubMedGoogle Scholar
  44. 44.
    Pohl S, Marschner K, Storch S, Braulke T. Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases. Biol Chem. 2009;390(7):521–7.  https://doi.org/10.1515/bc.2009.076.PubMedGoogle Scholar
  45. 45.
    Sleat DE, Della Valle MC, Zheng H, Moore DF, Lobel P. The mannose 6-phosphate glycoprotein proteome. J Proteome Res. 2008;7(7):3010–21.  https://doi.org/10.1021/pr800135v.PubMedCentralPubMedGoogle Scholar
  46. 46.
    von Figura K, Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem. 1986;55:167–93.  https://doi.org/10.1146/annurev.bi.55.070186.001123.Google Scholar
  47. 47.
    Herzog V. Secretion of sulfated thyroglobulin. Eur J Cell Biol. 1986;39(2):399–409.PubMedGoogle Scholar
  48. 48.
    Herzog V, Neumuller W, Holzmann B. Thyroglobulin, the major and obligatory exportable protein of thyroid follicle cells, carries the lysosomal recognition marker mannose-6-phosphate. EMBO J. 1987;6(3):555–60.PubMedCentralPubMedGoogle Scholar
  49. 49.
    Lemansky P, Herzog V. Endocytosis of thyroglobulin is not mediated by mannose-6-phosphate receptors in thyrocytes. Evidence for low-affinity-binding sites operating in the uptake of thyroglobulin. Eur J Biochem. 1992;209(1):111–9.PubMedGoogle Scholar
  50. 50.
    Scheel G, Herzog V. Mannose 6-phosphate receptor in porcine thyroid follicle cells. Localization and possible implications for the intracellular transport of thyroglobulin. Eur J Cell Biol. 1989;49(1):140–8.PubMedGoogle Scholar
  51. 51.
    Bjorkman U, Ekholm R. Effect of tunicamycin on thyroglobulin secretion. Eur J Biochem. 1982;125(3):585–91.PubMedGoogle Scholar
  52. 52.
    Eggo MC, Burrow GN. Glycosylation of thyroglobulin—its role in secretion, iodination, and stability. Endocrinology. 1983;113(5):1655–63.  https://doi.org/10.1210/endo-113-5-1655.PubMedGoogle Scholar
  53. 53.
    Franc J-L, Hovespian S, Fayet G, Bouchilloux S. Inhibition of N-linked oligosaccharide processing does not prevent the secretion of thyroglobulin. Eur J Biochem. 1986;157(1):225–32.  https://doi.org/10.1111/j.1432-1033.1986.tb09660.x.PubMedGoogle Scholar
  54. 54.
    Lamas L, Anderson PC, Fox JW, Dunn JT. Consensus sequences for early iodination and hormonogenesis in human thyroglobulin. J Biol Chem. 1989;264(23):13541–5.PubMedGoogle Scholar
  55. 55.
    Studer H, von Grunigen C, Haeberli A, Kohler H, Rothlisberger M, Gerber H. Iodination of thyroglobulin molecules depends on their diffusion velocity in follicular colloid. Mol Cell Endocrinol. 1986;45(2–3):91–103.PubMedGoogle Scholar
  56. 56.
    Baumeister FA, Herzog V. Sulfation of thyroglobulin: a ubiquitous modification in vertebrates. Cell Tissue Res. 1988;252(2):349–58.PubMedGoogle Scholar
  57. 57.
    Cauvi D, Venot N, Nlend MC, Chabaud OM. Thyrotropin and iodide regulate sulfate concentration in thyroid cells. Relationship to thyroglobulin sulfation. Can J Physiol Pharmacol. 2003;81(12):1131–8.  https://doi.org/10.1139/y03-120.PubMedGoogle Scholar
  58. 58.
    Venot N, Nlend MC, Cauvi D, Chabaud O. The hormonogenic tyrosine 5 of porcine thyroglobulin is sulfated. Biochem Biophys Res Commun. 2002;298(2):193–7.PubMedGoogle Scholar
  59. 59.
    Emoto N, Kunii YK, Ashizawa M, Oikawa S, Shimizu K, Shimonaka M, Toyoda A, Toyoda H. Reduced sulfation of chondroitin sulfate in thyroglobulin derived from human papillary thyroid carcinomas. Cancer Sci. 2007;98(10):1577–81.  https://doi.org/10.1111/j.1349-7006.2007.00574.x.PubMedGoogle Scholar
  60. 60.
    Baudry N, Lejeune P-J, Delom F, Vinet L, Carayon P, Mallet B. Role of multimerized porcine thyroglobulin in iodine storage. Biochem Biophys Res Commun. 1998;242(2):292–6.  https://doi.org/10.1006/bbrc.1997.7952.PubMedGoogle Scholar
  61. 61.
    Berndorfer U, Wilms H, Herzog V. Multimerization of thyroglobulin (TG) during extracellular storage: isolation of highly cross-linked TG from human thyroids. J Clin Endocrinol Metab. 1996;81(5):1918–26.  https://doi.org/10.1210/jcem.81.5.8626858.PubMedGoogle Scholar
  62. 62.
    Herzog V, Berndorfer U, Saber Y. Isolation of insoluble secretory product from bovine thyroid: extracellular storage of thyroglobulin in covalently cross-linked form. J Cell Biol. 1992;118(5):1071–83.PubMedGoogle Scholar
  63. 63.
    Klein M, Gestmann I, Berndorfer U, Schmitz A, Herzog V. The thioredoxin boxes of thyroglobulin: possible implications for intermolecular disulfide bond formation in the follicle lumen. Biol Chem. 2000;381(7):593–601.  https://doi.org/10.1515/bc.2000.076.PubMedGoogle Scholar
  64. 64.
    Saber-Lichtenberg Y, Brix K, Schmitz A, Heuser JE, Wilson JH, Lorand L, Herzog V. Covalent cross-linking of secreted bovine thyroglobulin by transglutaminase. FASEB J. 2000;14(7):1005–14.PubMedGoogle Scholar
  65. 65.
    Brix K, Lemansky P, Herzog V. Evidence for extracellularly acting cathepsins mediating thyroid hormone liberation in thyroid epithelial cells. Endocrinology. 1996;137(5):1963–74.  https://doi.org/10.1210/endo.137.5.8612537.PubMedGoogle Scholar
  66. 66.
    Brix K, Linke M, Tepel C, Herzog V. Cysteine proteinases mediate extracellular prohormone processing in the thyroid. Biol Chem. 2001;382(5):717–25.  https://doi.org/10.1515/bc.2001.087.PubMedGoogle Scholar
  67. 67.
    Dunn AD, Crutchfield HE, Dunn JT. Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. Endocrinology. 1991a;128(6):3073–80.  https://doi.org/10.1210/endo-128-6-3073.PubMedGoogle Scholar
  68. 68.
    Dunn AD, Crutchfield HE, Dunn JT. Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L. J Biol Chem. 1991b;266(30):20198–204.PubMedGoogle Scholar
  69. 69.
    Dunn AD, Dunn JT. Thyroglobulin degradation by thyroidal proteases: action of thiol endopeptidases in vitro. Endocrinology. 1982;111(1):290–8.  https://doi.org/10.1210/endo-111-1-290.PubMedGoogle Scholar
  70. 70.
    Dunn AD, Dunn JT. Cysteine proteinases from human thyroids and their actions on thyroglobulin. Endocrinology. 1988;123(2):1089–97.  https://doi.org/10.1210/endo-123-2-1089.PubMedGoogle Scholar
  71. 71.
    Friedrichs B, Tepel C, Reinheckel T, Deussing J, von Figura K, Herzog V, Peters C, Saftig P, Brix K. Thyroid functions of mouse cathepsins B, K, and L. J Clin Invest. 2003;111(11):1733–45.  https://doi.org/10.1172/jci15990.PubMedCentralPubMedGoogle Scholar
  72. 72.
    Jordans S, Jenko-Kokalj S, Kuhl NM, Tedelind S, Sendt W, Bromme D, Turk D, Brix K. Monitoring compartment-specific substrate cleavage by cathepsins B, K, L, and S at physiological pH and redox conditions. BMC Biochem. 2009;10:23.  https://doi.org/10.1186/1471-2091-10-23.PubMedCentralPubMedGoogle Scholar
  73. 73.
    Tepel C, Bromme D, Herzog V, Brix K. Cathepsin K in thyroid epithelial cells: sequence, localization and possible function in extracellular proteolysis of thyroglobulin. J Cell Sci. 2000;113(Pt 24):4487–98.PubMedGoogle Scholar
  74. 74.
    Romagnoli P, Herzog V. Transcytosis in thyroid follicle cells: regulation and implications for thyroglobulin transport. Exp Cell Res. 1991;194(2):202–9.PubMedGoogle Scholar
  75. 75.
    Pacini F, Pinchera A. Serum and tissue thyroglobulin measurement: clinical applications in thyroid disease. Biochimie. 1999;81(5):463–7.PubMedGoogle Scholar
  76. 76.
    Brix K, Herzog V. Extrathyroidal release of thyroid hormones from thyroglobulin by J774 mouse macrophages. J Clin Invest. 1994;93(4):1388–96.  https://doi.org/10.1172/JCI117115.PubMedCentralPubMedGoogle Scholar
  77. 77.
    Brix K, Summa W, Lottspeich F, Herzog V. Extracellularly occurring histone H1 mediates the binding of thyroglobulin to the cell surface of mouse macrophages. J Clin Investig. 1998;102(2):283–93.PubMedGoogle Scholar
  78. 78.
    Brix K, Wirtz R, Herzog V. Paracrine interaction between hepatocytes and macrophages after extrathyroidal proteolysis of thyroglobulin. Hepatology. 1997;26(5):1232–40.  https://doi.org/10.1053/jhep.1997.v26.pm0009362367.PubMedGoogle Scholar
  79. 79.
    Bizhanova A, Kopp P. Minireview: the sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology. 2009;150(3):1084–90.  https://doi.org/10.1210/en.2008-1437.PubMedCentralPubMedGoogle Scholar
  80. 80.
    de Vijlder JJ. Primary congenital hypothyroidism: defects in iodine pathways. Eur J Endocrinol. 2003;149(4):247–56.PubMedGoogle Scholar
  81. 81.
    Dunn JT, Dunn AD. Update on intrathyroidal iodine metabolism. Thyroid. 2001;11(5):407–14.  https://doi.org/10.1089/105072501300176363.PubMedGoogle Scholar
  82. 82.
    Gerard AC, Daumerie C, Mestdagh C, Gohy S, De Burbure C, Costagliola S, Miot F, Nollevaux MC, Denef JF, Rahier J, Franc B, De Vijlder JJ, Colin IM, Many MC. Correlation between the loss of thyroglobulin iodination and the expression of thyroid-specific proteins involved in iodine metabolism in thyroid carcinomas. J Clin Endocrinol Metab. 2003;88(10):4977–83.  https://doi.org/10.1210/jc.2003-030586.PubMedGoogle Scholar
  83. 83.
    Moreno JC, Visser TJ. New phenotypes in thyroid dyshormonogenesis: hypothyroidism due to DUOX2 mutations. Endocr Dev. 2007;10:99–117.  https://doi.org/10.1159/0000106822.PubMedGoogle Scholar
  84. 84.
    Nilsson M. Molecular and cellular mechanisms of transepithelial iodide transport in the thyroid. Biofactors. 1999;10(2–3):277–85.PubMedGoogle Scholar
  85. 85.
    Nilsson M. Iodide handling by the thyroid epithelial cell. Exp Clin Endocrinol Diabetes. 2001;109(1):13–7.  https://doi.org/10.1055/s-2001-11014.PubMedGoogle Scholar
  86. 86.
    Ohtaki S, Nakagawa H, Nakamura M, Kotani T. Thyroid peroxidase: experimental and clinical integration. Endocr J. 1996;43(1):1–14.PubMedGoogle Scholar
  87. 87.
    Ruf J, Carayon P. Structural and functional aspects of thyroid peroxidase. Arch Biochem Biophys. 2006;445(2):269–77.  https://doi.org/10.1016/j.abb.2005.06.023.PubMedGoogle Scholar
  88. 88.
    Morand S, Ueyama T, Tsujibe S, Saito N, Korzeniowska A, Leto TL. Duox maturation factors form cell surface complexes with Duox affecting the specificity of reactive oxygen species generation. FASEB J. 2009;23(4):1205–18.  https://doi.org/10.1096/fj.08-120006.PubMedCentralPubMedGoogle Scholar
  89. 89.
    Morrison M, Schonbaum GR. Peroxidase-catalyzed halogenation. Annu Rev Biochem. 1976;45:861–88.  https://doi.org/10.1146/annurev.bi.45.070176.004241.PubMedGoogle Scholar
  90. 90.
    Kohler H, Studer H, Gerber H, von Grunigen C. Experimental conditions leading to a low degree of thyroglobulin iodination without loss in coupling efficiency. Acta Endocrinol. 1982;100(1):36–40.PubMedGoogle Scholar
  91. 91.
    Turner CD, Chernoff SB, Taurog A, Rawitch AB. Differences in iodinated peptides and thyroid hormone formation after chemical and thyroid peroxidase-catalyzed iodination of human thyroglobulin. Arch Biochem Biophys. 1983;222(1):245–58.PubMedGoogle Scholar
  92. 92.
    Spitzweg C, Morris JC. Genetics and phenomics of hypothyroidism and goiter due to NIS mutations. Mol Cell Endocrinol. 2010;322(1–2):56–63.  https://doi.org/10.1016/j.mce.2010.02.007.PubMedCentralPubMedGoogle Scholar
  93. 93.
    Kopp P, Pesce L, Solis SJ. Pendred syndrome and iodide transport in the thyroid. Trends Endocrinol Metab. 2008;19(7):260–8.  https://doi.org/10.1016/j.tem.2008.07.001.PubMedGoogle Scholar
  94. 94.
    Silveira JC, Kopp PA. Pendrin and anoctamin as mediators of apical iodide efflux in thyroid cells. Curr Opin Endocrinol Diabetes Obes. 2015;22(5):374–80.  https://doi.org/10.1097/med.0000000000000188.PubMedGoogle Scholar
  95. 95.
    Rokita SE, Adler JM, McTamney PM, Watson JA Jr. Efficient use and recycling of the micronutrient iodide in mammals. Biochimie. 2010;92(9):1227–35.  https://doi.org/10.1016/j.biochi.2010.02.013.PubMedCentralPubMedGoogle Scholar
  96. 96.
    Song Y, Driessens N, Costa M, De Deken X, Detours V, Corvilain B, Maenhaut C, Miot F, Van Sande J, Many MC, Dumont JE. Roles of hydrogen peroxide in thyroid physiology and disease. J Clin Endocrinol Metab. 2007;92(10):3764–73.  https://doi.org/10.1210/jc.2007-0660.PubMedGoogle Scholar
  97. 97.
    Dunn JT. Thyroglobulin, hormone synthesis and thyroid disease. Eur J Endocrinol. 1995;132(5):603–4.PubMedGoogle Scholar
  98. 98.
    Dunn JT, Anderson PC, Fox JW, Fassler CA, Dunn AD, Hite LA, Moore RC. The sites of thyroid hormone formation in rabbit thyroglobulin. J Biol Chem. 1987;262(35):16948–52.PubMedGoogle Scholar
  99. 99.
    Hayden LJ, Shagrin JM, Young JA. Micropuncture investigation of the anion content of colloid from single rat thyroid follicles. Pflugers Arch. 1970;321(2):173–86.  https://doi.org/10.1007/bf00586371.PubMedGoogle Scholar
  100. 100.
    Smeds S. A microgel electrophoretic analysis of the colloid proteins in single rat thyroid follicles. II. The protein concentration of the colloid single rat thyroid follicles. Endocrinology. 1972;91(5):1300–6.  https://doi.org/10.1210/endo-91-5-1300.PubMedGoogle Scholar
  101. 101.
    Gerard AC, Denef JF, Colin IM, van den Hove MF. Evidence for processing of compact insoluble thyroglobulin globules in relation with follicular cell functional activity in the human and the mouse thyroid. Eur J Endocrinol. 2004;150(1):73–80.PubMedGoogle Scholar
  102. 102.
    Gerber H, Peter HJ, Studer H. Diffusion of thyroglobulin in the follicular colloid. (Minireview). Endocrinol Exp. 1986;20(1):23–33.PubMedGoogle Scholar
  103. 103.
    Giraud A, Dicristofaro J, De Micco C, Lejeune PJ, Barbaria J, Mallet B. A plasminogen-like protein, present in the apical extracellular environment of thyroid epithelial cells, degrades thyroglobulin in vitro. Biochem Biophys Res Commun. 2005;338(2):1000–4.  https://doi.org/10.1016/j.bbrc.2005.10.063.PubMedGoogle Scholar
  104. 104.
    Dauth S, Arampatzidou M, Rehders M, Yu DMT, Führer D, Brix K. Thyroid Cathepsin K: roles in physiology and thyroid disease. Clin Rev Bone Miner Metab. 2011;9(2):94–106.  https://doi.org/10.1007/s12018-011-9093-7.Google Scholar
  105. 105.
    De Robertis E. Proteolytic enzyme activity of colloid extracted from single follicles of the rat thyroid. Anat Rec. 1941;80(2):219–31.  https://doi.org/10.1002/ar.1090800208.Google Scholar
  106. 106.
    Linke M, Jordans S, Mach L, Herzog V, Brix K. Thyroid stimulating hormone upregulates secretion of cathepsin B from thyroid epithelial cells. Biol Chem. 2002;383(5):773–84.  https://doi.org/10.1515/bc.2002.081.PubMedGoogle Scholar
  107. 107.
    Giraud A, Lejeune PJ, Barbaria J, Mallet B. A plasminogen-like protease in thyroid rough microsomes degrades thyroperoxidase and thyroglobulin. Endocrinology. 2007;148(6):2886–93.  https://doi.org/10.1210/en.2007-0027.PubMedGoogle Scholar
  108. 108.
    Suban D, Zajc T, Renko M, Turk B, Turk V, Dolenc I. Cathepsin C and plasma glutamate carboxypeptidase secreted from Fischer rat thyroid cells liberate thyroxin from the N-terminus of thyroglobulin. Biochimie. 2012;94(3):719–26.  https://doi.org/10.1016/j.biochi.2011.10.018.PubMedGoogle Scholar
  109. 109.
    Brix K, Dunkhorst A, Mayer K, Jordans S. Cysteine cathepsins: cellular roadmap to different functions. Biochimie. 2008;90(2):194–207.  https://doi.org/10.1016/j.biochi.2007.07.024.PubMedGoogle Scholar
  110. 110.
    Brix K, McInnes J, Al-Hashimi A, Rehders M, Tamhane T, Haugen MH. Proteolysis mediated by cysteine cathepsins and legumain-recent advances and cell biological challenges. Protoplasma. 2015;252(3):755–74.  https://doi.org/10.1007/s00709-014-0730-0.PubMedGoogle Scholar
  111. 111.
    Brix K, Scott CJ, Heck MMS. Compartmentalization of proteolysis. In: Brix K, Stöcker W, editors. Proteases: structure and function. Wien: Springer-Verlag; 2013. p. 85–125.  https://doi.org/10.1007/978-3-7091-0885-7_3.Google Scholar
  112. 112.
    Brix K. Lysosomal proteases: revival of the sleeping beauty. In: Saftig P, editor. Madame Curie bioscience database (Internet). 2005.Google Scholar
  113. 113.
    Miot F, Dupuy C, Dumont JE, Rousset B. Chaper 2 thyroid hormone synthesis and secretion. Endotext (internet). MDText.com, Inc.; 2000, South Dartmouth, MA: Endocrine Education Inc; 2015. p. 02748.
  114. 114.
    Mohamed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer. 2006;6(10):764–75.  https://doi.org/10.1038/nrc1949.PubMedGoogle Scholar
  115. 115.
    Mort JS, Buttle DJ. Cathepsin B. Int J Biochem Cell Biol. 1997;29(5):715–20.PubMedGoogle Scholar
  116. 116.
    Sloane B, List K, Fingleton B, Matrisian L. Proteases in cancer: significance for invasion and metastasis. In: Brix K, Stöcker W, editors. Proteases: structure and function. Wien: Springer-Verlag; 2013. p. 491–550.  https://doi.org/10.1007/978-3-7091-0885-7_15.Google Scholar
  117. 117.
    Gaide Chevronnay HP, Janssens V, Van Der Smissen P, Liao XH, Abid Y, Nevo N, Antignac C, Refetoff S, Cherqui S, Pierreux CE, Courtoy PJ. A mouse model suggests two mechanisms for thyroid alterations in infantile cystinosis: decreased thyroglobulin synthesis due to endoplasmic reticulum stress/unfolded protein response and impaired lysosomal processing. Endocrinology. 2015;156(6):2349–64.  https://doi.org/10.1210/en.2014-1672.PubMedCentralPubMedGoogle Scholar
  118. 118.
    Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E. Cystinosis: a review. Orphanet J Rare Dis. 2016;11:47.  https://doi.org/10.1186/s13023-016-0426-y.PubMedCentralPubMedGoogle Scholar
  119. 119.
    Gaide Chevronnay HP, Janssens V, Van Der Smissen P, Rocca CJ, Liao XH, Refetoff S, Pierreux CE, Cherqui S, Courtoy PJ. Hematopoietic stem cells transplantation can normalize thyroid function in a cystinosis mouse model. Endocrinology. 2016;157(4):1363–71.  https://doi.org/10.1210/en.2015-1762.PubMedCentralPubMedGoogle Scholar
  120. 120.
    Bernier-Valentin F, Kostrouch Z, Rabilloud R, Munari-Silem Y, Rousset B. Coated vesicles from thyroid cells carry iodinated thyroglobulin molecules. First indication for an internalization of the thyroid prohormone via a mechanism of receptor-mediated endocytosis. J Biol Chem. 1990;265(28):17373–80.PubMedGoogle Scholar
  121. 121.
    Chambard M, Depetris D, Gruffat D, Gonzalvez S, Mauchamp J, Chabaud O. Thyrotrophin regulation of apical and basal exocytosis of thyroglobulin by porcine thyroid monolayers. J Mol Endocrinol. 1990;4(3):193–9.PubMedGoogle Scholar
  122. 122.
    Pierce LR, Zurzolo C, Salvatore G, Edelhoch H. Coated vesicles from the thyroid gland: isolation, characterization, and a search for a possible role in thyroglobulin transport. J Endocrinol Investig. 1985;8(4):303–12.  https://doi.org/10.1007/bf03348502.Google Scholar
  123. 123.
    Marino M, McCluskey RT. Role of thyroglobulin endocytic pathways in the control of thyroid hormone release. Am J Physiol Cell Physiol. 2000;279(5):C1295–306.PubMedGoogle Scholar
  124. 124.
    Mezghrani A, Courageot J, Mani JC, Pugniere M, Bastiani P, Miquelis R. Protein-disulfide isomerase (PDI) in FRTL5 cells. pH-dependent thyroglobulin/PDI interactions determine a novel PDI function in the post-endoplasmic reticulum of thyrocytes. J Biol Chem. 2000;275(3):1920–9.PubMedGoogle Scholar
  125. 125.
    Miquelis R, Courageot J, Jacq A, Blanck O, Perrin C, Bastiani P. Intracellular routing of GLcNAc-bearing molecules in thyrocytes: selective recycling through the Golgi apparatus. J Cell Biol. 1993;123(6 Pt 2):1695–706.PubMedGoogle Scholar
  126. 126.
    Lisi S, Madsen P, Botta R, Munck Petersen C, Nykjær A, Latrofa F, Vitti P, Marinò M. Absence of a thyroid phenotype in sortilin-deficient mice. Endocrine Practice. 2015;21(9):981–5.  https://doi.org/10.4158/EP15697.OR.PubMedGoogle Scholar
  127. 127.
    Herzog V. Transcytosis in thyroid follicle cells. J Cell Biol. 1983;97(3):607–17.PubMedGoogle Scholar
  128. 128.
    Mostov KE, Simister NE. Transcytosis. Cell. 1985;43(2 Pt 1):389–90.PubMedGoogle Scholar
  129. 129.
    Schneider PB. Thyroidal iodine heterogeneity: “last come, FIRST served” system of iodine turnover. Endocrinology. 1964;74:973–80.  https://doi.org/10.1210/endo-74-6-973.PubMedGoogle Scholar
  130. 130.
    Giraud A, Siffroi S, Lanet J, Franc JL. Binding and internalization of thyroglobulin: selectivity, pH dependence, and lack of tissue specificity. Endocrinology. 1997;138(6):2325–32.  https://doi.org/10.1210/endo.138.6.5195.PubMedGoogle Scholar
  131. 131.
    van den Hove MF, Couvreur M, de Visscher M, Salvatore G. A new mechanism for the reabsorption of thyroid iodoproteins: selective fluid pinocytosis. Eur J Biochem. 1982;122(2):415–22.PubMedGoogle Scholar
  132. 132.
    Consiglio E, Salvatore G, Rall JE, Kohn LD. Thyroglobulin interactions with thyroid plasma membranes. The existence of specific receptors and their potential role. J Biol Chem. 1979;254(12):5065–76.PubMedGoogle Scholar
  133. 133.
    Pacifico F, Liguoro D, Acquaviva R, Formisano S, Consiglio E. Thyroglobulin binding and TSH regulation of the RHL-1 subunit of the asialoglycoprotein receptor in rat thyroid. Biochimie. 1999;81(5):493–6.PubMedGoogle Scholar
  134. 134.
    Roitt IM, Pujol-Borrell R, Hanafusa T, Delves PJ, Bottazzo GF, Kohn LD. Asialoagalactothyroglobulin binds to the surface of human thyroid cells at a site distinct from the ‘microsomal’ autoantigen. Clin Exp Immunol. 1984;56(1):129–34.PubMedCentralPubMedGoogle Scholar
  135. 135.
    Suzuki K, Lavaroni S, Mori A, Ohta M, Saito J, Pietrarelli M, Singer DS, Kimura S, Katoh R, Kawaoi A, Kohn LD. Autoregulation of thyroid-specific gene transcription by thyroglobulin. Proc Natl Acad Sci U S A. 1998;95(14):8251–6.PubMedCentralPubMedGoogle Scholar
  136. 136.
    Ulianich L, Suzuki K, Mori A, Nakazato M, Pietrarelli M, Goldsmith P, Pacifico F, Consiglio E, Formisano S, Kohn LD. Follicular thyroglobulin (TG) suppression of thyroid-restricted genes involves the apical membrane asialoglycoprotein receptor and TG phosphorylation. J Biol Chem. 1999;274(35):25099–107.PubMedGoogle Scholar
  137. 137.
    Willnow TE, Nykjaer A, Herz J. Lipoprotein receptors: new roles for ancient proteins. Nat Cell Biol. 1999;1(6):E157–62.  https://doi.org/10.1038/14109.PubMedGoogle Scholar
  138. 138.
    Marino M, Zheng G, McCluskey RT. Megalin (gp330) is an endocytic receptor for thyroglobulin on cultured fisher rat thyroid cells. J Biol Chem. 1999;274(18):12898–904.PubMedGoogle Scholar
  139. 139.
    Zheng G, Bachinsky DR, Stamenkovic I, Strickland DK, Brown D, Andres G, McCluskey RT. Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP/alpha 2MR, and the receptor-associated protein (RAP). J Histochem Cytochem. 1994;42(4):531–42.PubMedGoogle Scholar
  140. 140.
    Zheng G, Marino M, Zhao J, McCluskey RT. Megalin (gp330): a putative endocytic receptor for thyroglobulin (Tg). Endocrinology. 1998;139(3):1462–5.  https://doi.org/10.1210/endo.139.3.5978.PubMedGoogle Scholar
  141. 141.
    Teumer A, Rawal R, Homuth G, Ernst F, Heier M, Evert M, Dombrowski F, Volker U, Nauck M, Radke D, Ittermann T, Biffar R, Doring A, Gieger C, Klopp N, Wichmann HE, Wallaschofski H, Meisinger C, Volzke H. Genome-wide association study identifies four genetic loci associated with thyroid volume and goiter risk. Am J Hum Genet. 2011;88(5):664–73.  https://doi.org/10.1016/j.ajhg.2011.04.015.PubMedCentralPubMedGoogle Scholar
  142. 142.
    Rawal R, Teumer A, Volzke H, Wallaschofski H, Ittermann T, Asvold BO, Bjoro T, Greiser KH, Tiller D, Werdan K, Meyer zu Schwabedissen HE, Doering A, Illig T, Gieger C, Meisinger C, Homuth G. Meta-analysis of two genome-wide association studies identifies four genetic loci associated with thyroid function. Hum Mol Genet. 2012;21(14):3275–82.  https://doi.org/10.1093/hmg/dds136.PubMedGoogle Scholar
  143. 143.
    Neve P, Willems C, Dumont JE. Involvement of the microtubule-microfilament system in thyroid secretion. Exp Cell Res. 1970;63(2):457–60.PubMedGoogle Scholar
  144. 144.
    Wetzel BK, Spicer SS, Wollman SH. Changes in fine structure and acid phosphatase localization in rat thyroid cells following thyrotropin administration. J Cell Biol. 1965;25(3):593–618.PubMedCentralPubMedGoogle Scholar
  145. 145.
    Fliers E, Kalsbeek A, Boelen A. Beyond the fixed setpoint of the hypothalamus-pituitary-thyroid axis. Eur J Endocrinol. 2014;171(5):R197–208.  https://doi.org/10.1530/eje-14-0285.PubMedCentralPubMedGoogle Scholar
  146. 146.
    Loosfelt H, Pichon C, Jolivet A, Misrahi M, Caillou B, Jamous M, Vannier B, Milgrom E. Two-subunit structure of the human thyrotropin receptor. Proc Natl Acad Sci U S A. 1992;89(9):3765–9.PubMedCentralPubMedGoogle Scholar
  147. 147.
    Kleinau G, Neumann S, Gruters A, Krude H, Biebermann H. Novel insights on thyroid-stimulating hormone receptor signal transduction. Endocr Rev. 2013;34(5):691–724.  https://doi.org/10.1210/er.2012-1072.PubMedCentralPubMedGoogle Scholar
  148. 148.
    Chiovato L, Pinchera A. The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. Autoimmunity. 1991;10(4):319–31.PubMedGoogle Scholar
  149. 149.
    Dumont JE, Maenhaut C, Lamy F. Control of thyroid cell proliferation and goitrogenesis. Trends Endocrinol Metab. 1992;3(1):12–7.PubMedGoogle Scholar
  150. 150.
    Ericson LE, Johansson BR. Early effects of thyroid stimulating hormone (TSH) on exocytosis and endocytosis in the thyroid. Acta Endocrinol. 1977;86(1):112–8.PubMedGoogle Scholar
  151. 151.
    Linke M, Herzog V, Brix K. Trafficking of lysosomal cathepsin B-green fluorescent protein to the surface of thyroid epithelial cells involves the endosomal/lysosomal compartment. J Cell Sci. 2002;115(Pt 24):4877–89.PubMedGoogle Scholar
  152. 152.
    Chabaud O, Chambard M, Gaudry N, Mauchamp J. Thyrotrophin and cyclic AMP regulation of thyroglobulin gene expression in cultured porcine thyroid cells. J Endocrinol. 1988;116(1):25–33.PubMedGoogle Scholar
  153. 153.
    Dunn AD. Stimulation of thyroidal thiol endopeptidases by thyrotropin. Endocrinology. 1984;114(2):375–82.  https://doi.org/10.1210/endo-114-2-375.PubMedGoogle Scholar
  154. 154.
    Petanceska S, Devi L. Sequence analysis, tissue distribution, and expression of rat cathepsin S. J Biol Chem. 1992;267(36):26038–43.PubMedGoogle Scholar
  155. 155.
    Phillips ID, Black EG, Sheppard MC, Docherty K. Thyrotrophin, forskolin and ionomycin increase cathepsin B mRNA concentrations in rat thyroid cells in culture. J Mol Endocrinol. 1989;2(3):207–12.PubMedGoogle Scholar
  156. 156.
    Lenarcic B, Turk V. Thyroglobulin type-1 domains in equistatin inhibit both papain-like cysteine proteinases and cathepsin D. J Biol Chem. 1999;274(2):563–6.PubMedGoogle Scholar
  157. 157.
    Mihelic M, Turk D. Two decades of thyroglobulin type-1 domain research. Biol Chem. 2007;388(11):1123–30.  https://doi.org/10.1515/bc.2007.155.PubMedGoogle Scholar
  158. 158.
    Pungercic G, Dolenc I, Dolinar M, Bevec T, Jenko S, Kolaric S, Turk V. Individual recombinant thyroglobulin type-1 domains are substrates for lysosomal cysteine proteinases. Biol Chem. 2002;383(11):1809–12.  https://doi.org/10.1515/bc.2002.202.PubMedGoogle Scholar
  159. 159.
    Molina F, Pau B, Granier C. The type-1 repeats of thyroglobulin regulate thyroglobulin degradation and T3, T4 release in thyrocytes. FEBS Lett. 1996;391(3):229–31.PubMedGoogle Scholar
  160. 160.
    Herz J, Strickland DK. LRP: a multifunctional scavenger and signaling receptor. J Clin Invest. 2001;108(6):779–84.  https://doi.org/10.1172/jci13992.PubMedCentralPubMedGoogle Scholar
  161. 161.
    Troeberg L, Lazenbatt C, Anower EKMF, Freeman C, Federov O, Habuchi H, Habuchi O, Kimata K, Nagase H. Sulfated glycosaminoglycans control the extracellular trafficking and the activity of the metalloprotease inhibitor TIMP-3. Chem Biol. 2014;21(10):1300–9.  https://doi.org/10.1016/j.chembiol.2014.07.014.PubMedCentralPubMedGoogle Scholar
  162. 162.
    Yamamoto K, Troeberg L, Scilabra SD, Pelosi M, Murphy CL, Strickland DK, Nagase H. LRP-1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage. FASEB J. 2013;27(2):511–21.  https://doi.org/10.1096/fj.12-216671.PubMedCentralPubMedGoogle Scholar
  163. 163.
    Lemansky P, Brix K, Herzog V. Subcellular distribution, secretion, and posttranslational modifications of clusterin in thyrocytes. Exp Cell Res. 1999;251(1):147–55.  https://doi.org/10.1006/excr.1999.4555.PubMedGoogle Scholar
  164. 164.
    Luo Y, Ishido Y, Hiroi N, Ishii N, Suzuki K. The emerging roles of thyroglobulin. Adv Endocrinol. 2014;2014:7.  https://doi.org/10.1155/2014/189194.Google Scholar
  165. 165.
    Sellitti DF, Suzuki K. Intrinsic regulation of thyroid function by thyroglobulin. Thyroid. 2014;24(4):625–38.  https://doi.org/10.1089/thy.2013.0344.PubMedCentralPubMedGoogle Scholar
  166. 166.
    Suzuki K, Kawashima A, Yoshihara A, Akama T, Sue M, Yoshida A, Kimura HJ. Role of thyroglobulin on negative feedback autoregulation of thyroid follicular function and growth. J Endocrinol. 2011;209(2):169–74.  https://doi.org/10.1530/joe-10-0486.PubMedGoogle Scholar
  167. 167.
    Suzuki K, Mori A, Lavaroni S, Katoh R, Kohn LD, Kawaoi A. Thyroglobulin: a master regulator of follicular function via transcriptional suppression of thyroid specific genes. Acta Histochem Cytochem. 1999a;32(2):111–9.  https://doi.org/10.1267/ahc.32.111.Google Scholar
  168. 168.
    Suzuki K, Mori A, Lavaroni S, Miyagi E, Ulianich L, Katoh R, Kawaoi A, Kohn LD. In vivo expression of thyroid transcription factor-1 RNA and its relation to thyroid function and follicular heterogeneity: identification of follicular thyroglobulin as a feedback suppressor of thyroid transcription factor-1 RNA levels and thyroglobulin synthesis. Thyroid. 1999b;9(4):319–31.  https://doi.org/10.1089/thy.1999.9.319.PubMedGoogle Scholar
  169. 169.
    Suzuki K, Mori A, Saito J, Moriyama E, Ullianich L, Kohn LD. Follicular thyroglobulin suppresses iodide uptake by suppressing expression of the sodium/iodide symporter gene. Endocrinology. 1999c;140(11):5422–30.  https://doi.org/10.1210/endo.140.11.7124.PubMedGoogle Scholar
  170. 170.
    Eng PH, Cardona GR, Fang SL, Previti M, Alex S, Carrasco N, Chin WW, Braverman LE. Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology. 1999;140(8):3404–10.  https://doi.org/10.1210/endo.140.8.6893.PubMedGoogle Scholar
  171. 171.
    Lemansky P, Brix K, Herzog V. Iodination of mature cathepsin D in thyrocytes as an indicator for its transport to the cell surface. Eur J Cell Biol. 1998;76(1):53–62.  https://doi.org/10.1016/s0171-9335(98)80017-4.PubMedGoogle Scholar
  172. 172.
    Braun D, Wirth EK, Schweizer U. Thyroid hormone transporters in the brain. Rev Neurosci. 2010;21(3):173–86.PubMedGoogle Scholar
  173. 173.
    Friesema EC, Docter R, Moerings EP, Verrey F, Krenning EP, Hennemann G, Visser TJ. Thyroid hormone transport by the heterodimeric human system L amino acid transporter. Endocrinology. 2001;142(10):4339–48.  https://doi.org/10.1210/endo.142.10.8418.PubMedGoogle Scholar
  174. 174.
    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(41):40128–35.  https://doi.org/10.1074/jbc.M300909200.PubMedCentralPubMedGoogle Scholar
  175. 175.
    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(4):451–76.  https://doi.org/10.1210/edrv.22.4.0435.PubMedCentralPubMedGoogle Scholar
  176. 176.
    Heuer H, Visser TJ. Minireview: pathophysiological importance of thyroid hormone transporters. Endocrinology. 2009;150(3):1078–83.  https://doi.org/10.1210/en.2008-1518.PubMedGoogle Scholar
  177. 177.
    Horn S, Heuer H. Thyroid hormone action during brain development: more questions than answers. Mol Cell Endocrinol. 2010;315(1–2):19–26.  https://doi.org/10.1016/j.mce.2009.09.008.PubMedGoogle Scholar
  178. 178.
    Kinne A, Kleinau G, Hoefig CS, Gruters A, Kohrle J, Krause G, Schweizer U. Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8. J Biol Chem. 2010;285(36):28054–63.  https://doi.org/10.1074/jbc.M110.129577.PubMedCentralPubMedGoogle Scholar
  179. 179.
    Kinne A, Schulein R, Krause G. Primary and secondary thyroid hormone transporters. Thyroid Res. 2011;4(Suppl 1):S7.  https://doi.org/10.1186/1756-6614-4-s1-s7.PubMedCentralPubMedGoogle Scholar
  180. 180.
    Laurberg P. Mechanisms governing the relative proportions of thyroxine and 3,5,3′-triiodothyronine in thyroid secretion. Metab Clin Exp. 1984;33(4):379–92.PubMedGoogle Scholar
  181. 181.
    Ritchie JW, Taylor PM. Role of the system L permease LAT1 in amino acid and iodothyronine transport in placenta. Biochem J. 2001;356(Pt 3):719–25.PubMedCentralPubMedGoogle Scholar
  182. 182.
    Sugiyama D, Kusuhara H, Taniguchi H, Ishikawa S, Nozaki Y, Aburatani H, Sugiyama Y. Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine. J Biol Chem. 2003;278(44):43489–95.  https://doi.org/10.1074/jbc.M306933200.PubMedCentralPubMedGoogle Scholar
  183. 183.
    Trajkovic-Arsic M, Muller J, Darras VM, Groba C, Lee S, Weih D, Bauer K, Visser TJ, Heuer H. Impact of monocarboxylate transporter-8 deficiency on the hypothalamus-pituitary-thyroid axis in mice. Endocrinology. 2010a;151(10):5053–62.  https://doi.org/10.1210/en.2010-0593.PubMedCentralPubMedGoogle Scholar
  184. 184.
    Trajkovic-Arsic M, Visser TJ, Darras VM, Friesema EC, Schlott B, Mittag J, Bauer K, Heuer H. Consequences of monocarboxylate transporter 8 deficiency for renal transport and metabolism of thyroid hormones in mice. Endocrinology. 2010b;151(2):802–9.  https://doi.org/10.1210/en.2009-1053.PubMedCentralPubMedGoogle Scholar
  185. 185.
    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(3):627–35.  https://doi.org/10.1172/JCI28253.PubMedCentralPubMedGoogle Scholar
  186. 186.
    Visser WE, Friesema EC, Jansen J, Visser TJ. Thyroid hormone transport by monocarboxylate transporters. Best Pract Res Clin Endocrinol Metab. 2007;21(2):223–36.  https://doi.org/10.1016/j.beem.2007.03.008.PubMedGoogle Scholar
  187. 187.
    Wirth EK, Roth S, Blechschmidt C, Holter SM, Becker L, Racz I, Zimmer A, Klopstock T, Gailus-Durner V, Fuchs H, Wurst W, Naumann T, Brauer A, de Angelis MH, Kohrle J, Gruters A, Schweizer U. 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(30):9439–49.  https://doi.org/10.1523/jneurosci.6055-08.2009.PubMedCentralPubMedGoogle Scholar
  188. 188.
    Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet. 2004;364(9443):1435–7.  https://doi.org/10.1016/s0140-6736(04)17226-7.PubMedCentralPubMedGoogle Scholar
  189. 189.
    Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, Ward J, Sanabria J, Marsa S, Lewis JA, Echeverri R, Lubs HA, Voeller K, Simensen RJ, Stevenson RE. Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet. 2005;77(1):41–53.  https://doi.org/10.1086/431313.PubMedCentralPubMedGoogle Scholar
  190. 190.
    Wirth EK, Sheu SY, Chiu-Ugalde J, Sapin R, Klein MO, Mossbrugger I, Quintanilla-Martinez L, de Angelis MH, Krude H, Riebel T, Rothe K, Kohrle J, Schmid KW, Schweizer U, Gruters A. Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy. Eur J Endocrinol. 2011;165(4):555–61.  https://doi.org/10.1530/eje-11-0369.PubMedGoogle Scholar
  191. 191.
    Müller J, Heuer H. Expression pattern of thyroid hormone transporters in the postnatal mouse brain. Front Endocrinol. 2014;5:92.  https://doi.org/10.3389/fendo.2014.00092.Google Scholar
  192. 192.
    Braun D, Wirth EK, Wohlgemuth F, Reix N, Klein MO, Gruters A, Kohrle J, Schweizer U. Aminoaciduria, but normal thyroid hormone levels and signalling, in mice lacking the amino acid and thyroid hormone transporter Slc7a8. Biochem J. 2011;439(2):249–55.  https://doi.org/10.1042/bj20110759.PubMedGoogle Scholar
  193. 193.
    Di Cosmo C, Liao XH, Dumitrescu AM, Philp NJ, Weiss RE, Refetoff S. Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion. J Clin Invest. 2010;120(9):3377–88.  https://doi.org/10.1172/jci42113.PubMedCentralPubMedGoogle Scholar
  194. 194.
    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(9):4036–43.  https://doi.org/10.1210/en.2006-0390.PubMedGoogle Scholar
  195. 195.
    Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies. Drug Metab Pharmacokinet. 2008;23(1):22–44.PubMedGoogle Scholar
  196. 196.
    Führer D, Brix K, Biebermann H. Understanding the healthy thyroid state in 2015. Eur Thyroid J. 2015;4(Suppl 1):1–8.  https://doi.org/10.1159/000431318.PubMedCentralPubMedGoogle Scholar
  197. 197.
    Mc Innes J, Weber J, Rehders M, Saftig P, Peters C, Reinheckel T, Schweizer U, Heuer H, Wirth EK, Brix K. Correlation of the expression and localization of thyroid hormone transporters with thyroglobulin-processing cathepsins in mouse thyroid epithelial cells. Presented at the 37th Annual Meeting of the European Thyroid Association, Leiden, The Netherlands, September 7–11, 2013. Abstracts. Eur Thyroid J. 2013;2(Suppl 1):90–1, OP45.  https://doi.org/10.1159/000352096.Google Scholar
  198. 198.
    Boland D, Weber J, Rehders M, Rodermund L, Heuer H, Brix K. Functional and morphological phenotypes in the mouse thyroid gland associated with thyroid-specific Mct8 deficiency. EJEA Endoc Abst. 2016;41:GP190.  https://doi.org/10.1530/endoabs.41.gp190.Google Scholar
  199. 199.
    Weber J, McInnes J, Kizilirmak C, Rehders M, Qatato M, Wirth EK, Schweizer U, Verrey F, Heuer H, Brix K. Interdependence of thyroglobulin processing and thyroid hormone export in the mouse thyroid gland. Eur J Cell Biol. 2017;96:440–56.  https://doi.org/10.1016/j.ejcb.2017.02.002.PubMedGoogle Scholar
  200. 200.
    Szumska J, Qatato M, Rehders M, Führer D, Biebermann H, Grandy DK, Köhrle J, Brix K. Trace amine-associated receptor 1 localization at the apical plasma membrane domain of fisher rat thyroid epithelial cells is confined to cilia. Eur Thyroid J. 2015;4(Suppl 1):30–41.  https://doi.org/10.1159/000434717.PubMedCentralPubMedGoogle Scholar
  201. 201.
    Qatato M, Szumska J, Skripnik V, Rijntjes E, Köhrle J, Brix K. Cannonical. TSH regulation of cathepsin-mediated thyroglobulin processing in the thyroid gland of male mice requires Taar1 expression. Frontiers Pharmacol. 2018;9:Article 221.  https://doi.org/10.3389/fphar.2018.00221.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Klaudia Brix
    • 1
    Email author
  • Maria Qatato
    • 1
  • Joanna Szumska
    • 1
  • Vaishnavi Venugopalan
    • 1
  • Maren Rehders
    • 1
  1. 1.Department of Life Sciences and ChemistryJacobs University BremenBremenGermany

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