Iodide handling by the thyroid epithelial cell

 

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Summary:

Iodination of thyroglobulin, the key event in the synthesis of thyroid hormone, is an extracellular process that takes place inside the thyroid follicles at the apical membrane surface that faces the follicular lumen. The supply of iodide involves two steps of TSH-regulated transport, basolateral uptake and apical efflux, that imprint the polarized phenotype of the thyroid cell. Iodide uptake is generated by the sodium/iodide symporter present in the basolateral plasma membrane. A candidate for the apical iodide-permeating mechanism is pendrin, a chloride/iodide transporting protein recently identified in the apical membrane. In physiological conditions, transepithelial iodide transport occurs without intracellular iodination, despite the presence of large amounts of thyroglobulin and thyroperoxidase inside the cells. The reason is that hydrogen peroxide, serving as electron acceptor in iodide-protein binding and normally produced at the apical cell surface, is rapidly degraded by cytosolic glutathione peroxidase once it enters the cells. Iodinated thyroglobulin in the lumen stores not only thyroid hormone but iodine incorporated in iodotyrosine residues as well. After endocytic uptake and degradation of thyroglobulin, intracellular deiodination provides a mechanism for recycling of iodide to participate in the synthesis of new thyroid hormone at the apical cell surface.

References

• 1 Amphoux-Fazekas T, Samih N, Hovsepian S, Aouani A, Beauwens R, Fayet G. DIDS (4,4′-diisothiocyantostilbene-2,2′-disulfonic acid) increases iodide trapping, inhibits thyroperoxidase and antagonizes the TSH-induced apical iodide efflux in porcine thyroid cells.  Mol Cell Endocrinol. 141 129-140 1998; 
  CrossrefPubMedGoogle Scholar
• 2 Andros G, Wollman S H. Autoradiographic localization of radioiodide in the thyroid gland of the mouse.  Am J Physiol. 213 198-208 1967; 
  PubMedGoogle Scholar
• 3 Carrasco N. Iodide transport in the thyroid gland.  Biochim Biophys Acta. 1154 65-82 1993; 
  PubMedGoogle Scholar
• 4 Balda M S, Matter K. Tight junctions.  J Cell Sci. 111 541-547 1998; 
  PubMedGoogle Scholar
• 5 Bidart J M, Mian C, Lazar V, Russo D, Filetti S, Caillou B, Schlumberger M. Expression of pendrin and the Pendred syndrome (PDS) gene in human thyroid tissues.  J Clin Endocrinol Metab. 85 2028-2033 2000; 
  CrossrefPubMedGoogle Scholar
• 6 Björkman U, Ekholm R. Hydrogen peroxide degradation and glutathione peroxidase activity in cultures of thyroid cells.  Mol Cell Endocrinol. 111 99-107 1995; 
  CrossrefPubMedGoogle Scholar
• 7 Boeynaems J M, Van Sande J, Dumont J E. Which iodolipids are involved in thyroid autoregulation: iodolactones or iodoaldehydes?.  Eur J Endocrinol. 132 733-734 1995; 
  PubMedGoogle Scholar
• 8 Brix K, Lemansky P, Herzog V. Evidence for extracellularly acting cathepsins mediating thyroid hormone liberation in thyroid epithelial cells.  Endocrinology. 137 1963-1974 1996; 
  CrossrefPubMedGoogle Scholar
• 9 Cereijido M, Valdes J, Shoshani L, Contreras R G. Role of tight junctions in establishing and maintaining cell polarity.  Annu Rev Physiol. 60 161-177 1998; 
  CrossrefPubMedGoogle Scholar
• 10 Chambard M, Verrier J, Gabrion J, Mauchamp J. Polarization of thyroid cells in culture. Evidence for the basolateral localization of the “iodide pump” and of the thyroid-stimulating hormone receptor-adenylate cyclase complex.  J Cell Biol. 96 1172-1177 1983; 
  CrossrefPubMedGoogle Scholar
• 11 Contempre B, Denef J F, Dumont J E, Many M C. Selenium deficiency aggravates the necrotizing effects of a high iodide dose in iodine deficient rats.  Endocrinology. 132 163-166 1993; 
  PubMedGoogle Scholar
• 12 De la Vieja A, Dohan O, Levy O, Carrasco N. Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology.  Physiol Rev. 80 1083-1105 2000; 
  PubMedGoogle Scholar
• 13 Denef J F, Many M C, van den Hove M F. Iodine-induced thyroid inhibition and cell necrosis: two consequences of the same free radical mediated mechanism?.  Mol Cell Endocrinol. 121 101-103 1996; 
  CrossrefPubMedGoogle Scholar
• 14 Ekholm R, Wollman S H. Site of iodination in rat thyroid gland deduced from electron microscopic autoradiographs.  Endocrinology. 97 1432-1444 1975; 
  PubMedGoogle Scholar
• 15 Ekholm R. Iodination of thyroglobulin, an intracellular or extracellular process?.  Mol Cell Endocrinol. 24 141-163 1981; 
  CrossrefPubMedGoogle Scholar
• 16 Ekholm R, Björkman U. Localization of iodide binding in the thyroid gland in vitro.  Endocrinology. 115 1558-1567 1984; 
  PubMedGoogle Scholar
• 17 Ekholm R. Biosynthesis of thyroid hormones.  Int Rev Cytol. 120 243-288 1990; 
  PubMedGoogle Scholar
• 18 Ekholm R, Björkman U. Glutathione peroxidase degrades intracellular hydrogen peroxide and thereby inhibits intracellular protein iodination in thyroid epithelium.  Endocrinology. 138 2871-2878 1997; 
  CrossrefPubMedGoogle Scholar
• 19 Ericson L E, Nilsson M. Effect of IGF-1 on growth, epithelial barrier and iodide transport in polarized porcine thyrocyte monolayers.  Eur J Endocrinol. 135 118-127 1996; 
  PubMedGoogle Scholar
• 20 Gerard C, Gabrion J, Verrier B, Reggio H, Mauchamp J. Localization of the Na⁺/K⁺ ATPase and of an amiloride sensitive Na⁺ uptake on thyroid epithelial cells.  Eur J Cell Biol. 38 134-141 1985; 
  PubMedGoogle Scholar
• 21 Halmi N S. Thyroidal iodide transport.  Vitam Horm. 19 133-162 1961; 
  PubMedGoogle Scholar
• 22 Nilsson M, Björkman U, Ekholm R, Ericson L E. Iodide transport in primary cultured thyroid follicle cells: evidence of a TSH-regulated channel mediating iodide efflux selectively across the apical domain of the plasma membrane.  Eur J Cell Biol. 52 270-281 1990; 
  PubMedGoogle Scholar
• 23 Nilsson M. Integrity of the occluding barrier in high-resistant thyroid follicular epithelium in culture. I. Dependence on extracellular Ca²⁺ is polarized.  Eur J Cell Biol. 56 295-307 1991; 
  PubMedGoogle Scholar
• 24 Nilsson M, Björkman U, Ekholm R, Ericson L E. Polarized efflux of iodide in porcine thyrocytes occurs via a cAMP-regulated iodide channel in the apical plasma membrane.  Acta Endocrinol. 126 67-74 1992; 
  PubMedGoogle Scholar
• 25 Nilsson M, Ericson L E. Effects of epidermal growth factor on basolateral iodide uptake and apical iodide permeability in filter-cultured thyroid epithelium.  Endocrinology. 135 1428-1436 1994; 
  CrossrefPubMedGoogle Scholar
• 26 Nilsson M. Molecular and cellular mechanisms of transepithelial iodide transport in the thyroid.  Biofactors. 10 277-285 1999; 
  PubMedGoogle Scholar
• 27 Royaux I E, Suzuki K, Mori A, Katoh R, Everett L A, Kohn L D, Green E D. Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells.  Endocrinology. 141 839-845 2000; 
  CrossrefPubMedGoogle Scholar
• 28 Scott D A, Wang R, Kreman T M, Sheffield V C, Karnishki L P. The Pendred syndrome gene encodes a chloride-iodide transport protein.  Nat Genet. 21 440-443 1999; 
  PubMedGoogle Scholar
• 29 Sheffield V C, Kraiem Z, Beck J C, Nishimura D, Stone E M, Salameh M, Sadeh O, Glaser B. Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification.  Nat Genet. 12 424-426 1996; 
  CrossrefPubMedGoogle Scholar
• 30 Spitzweg C, Heufelder A E, Morris J C. Thyroid iodine transport.  Thyroid. 10 321-330 2000; 
  PubMedGoogle Scholar
• 31 Wolff J. Transport of iodide and other anions in the thyroid gland.  Physiol Rev. 44 45-90 1964; 
  PubMedGoogle Scholar
• 32 Wolff J. Iodide goiter and the pharmacologic effects of excess iodide.  Am J Med. 47 101-124 1969; 
  CrossrefPubMedGoogle Scholar
• 33 Wollman S H. Thyroid radioiodide transport: models, rate-limiting steps, and relation to formation of iodoprotein.  Eur J Cell Biol. 66 217-225 1995; 
  PubMedGoogle Scholar

Mikael NilssonMD, PhD 

Institute of Anatomy and Cell Biology

Göteborg University

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Email: mikael.olof.nilsson@anatcell.gu.se