Fri . 19 Apr 2019

Thyroglobulin

thyroglobulin antibodies, thyroglobulin levels
NM_003235

NM_009375

RefSeq protein

NP_003226

NP_033401

Location UCSC Chr 8: 13287 – 13313 Mb Chr 15: 6667 – 6685 Mb PubMed search Wikidata
1 Function
  • 2 Clinical significance
    • 21 Half-life and clinical elevation
    • 22 Thyroglobulin antibodies
  • 3 Interactions
  • 4 References
  • 5 Further reading
  • 6 External links
  • Function

    Thyroid hormone synthesis, this image traces thyroglobulin from production within the rough endoplasmic reticulum until proteolytic release of the thyroid hormones

    Tg is used by the thyroid gland to produce the thyroid hormones thyroxine T4 and triiodothyronine T3 The active form of triiodothyronine, 3, 5, 3' triiodothyronine, is produced both within the thyroid gland and in the periphery by 5'-deiodinase which has been referred to as tetraiodothyronine 5' deiodinase It is presumed that Tg and thyroid are also an important storage of iodine for all body needs, in particular, for many iodine-concentrating organs such as breast, stomach, salivary glands, thymus, choroid plexus and cerebrospinal fluid, etc see iodine in biology

    Tg is produced by the thyroid epithelial cells, called thyrocytes, which form spherical follicles Tg is secreted and stored in the follicular lumen

    Via a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues in thyroglobulin molecules, forming monoiodotyrosine MIT and diiodotyrosine DIT

    • Thyroxine is produced by combining two moieties of DIT
    • Triiodothyronine is produced by combining one molecule of MIT and one molecule of DIT

    Small globules of the follicular colloid Tg are endocytosed hormone TSH-mediated and proteases in lysosomes digest iodinated thyroglobulin, releasing T3 and T4 within the thyrocyte cytoplasm The T3 and T4 are then transported across TSH-mediated the basolateral thyrocyte membrane, into the bloodstream, by an unknown mechanism, while the lysosome is recycled back to the follicular lumen

    Clinical significance

    Half-life and clinical elevation

    Metabolism of thyroglobulin occurs in the liver and via thyroid gland recycling of the protein Circulating thyroglobulin has a half-life of 65 hours Following thyroidectomy, it may take many weeks before thyroglobulin levels become undetectable After thyroglobulin levels become undetectable following thyroidectomy, levels can be serially monitored

    A subsequent elevation of the thyroglobulin level is an indication of recurrence of papillary or follicular thyroid carcinoma Hence, thyroglobulin levels in the blood are mainly used as a tumor marker for certain kinds of thyroid cancer particularly papillary or follicular thyroid cancer Thyroglobulin is not produced by medullary or anaplastic thyroid carcinoma

    Thyroglobulin antibodies

    In the clinical laboratory, thyroglobulin testing can be complicated by the presence of anti-thyroglobulin antibodies ATAs, alternatively referred to as TgAb Anti-thyroglobulin antibodies are present in 1 in 10 normal individuals, and a greater percentage of patients with thyroid carcinoma The presence of these antibodies can result in falsely low or rarely falsely high levels of reported thyroglobulin, a problem that can be somewhat circumvented by concomitant testing for the presence of ATAs The ideal strategy for a clinician's interpretation and management of patient care in the event of confounding detection of ATAs is testing to follow serial quantitative measurements rather than a single laboratory measurement

    ATAs are often found in patients with Hashimoto's thyroiditis or Graves' disease Their presence is of limited use in the diagnosis of these diseases, since they may also be present in healthy euthyroid individuals ATAs are also found in patients with Hashimoto's encephalopathy, a neuroendocrine disorder related to—but not caused by—Hashimoto's thyroiditis

    Interactions

    Thyroglobulin has been shown to interact with Binding immunoglobulin protein

    References

    1. ^ a b c GRCh38: Ensembl release 89: ENSG00000042832 - Ensembl, May 2017
    2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000053469 - Ensembl, May 2017
    3. ^ "Human PubMed Reference:" 
    4. ^ "Mouse PubMed Reference:" 
    5. ^ a b Boron WF 2003 Medical Physiology: A Cellular And Molecular Approach Elsevier/Saunders p 1044 ISBN 1-4160-2328-3 
    6. ^ cite web |url="https://wwwncbinlmnihgov/protein/NP_0032264"
    7. ^ Venturi S, Donati FM, Venturi A, Venturi M August 2000 "Environmental iodine deficiency: A challenge to the evolution of terrestrial life" Thyroid 10 8: 727–9 doi:101089/10507250050137851 PMID 11014322 
    8. ^ "ACS :: Tumor Markers" American Cancer Society Retrieved 2009-03-28 
    9. ^ Ferracci F, Moretto G, Candeago RM, Cimini N, Conte F, Gentile M, Papa N, Carnevale A February 2003 "Antithyroid antibodies in the CSF: Their role in the pathogenesis of Hashimoto's encephalopathy" Neurology 60 4: 712–4 doi:101212/01wnl000004866071390c6 PMID 12601119 
    10. ^ Delom F, Mallet B, Carayon P, Lejeune PJ June 2001 "Role of extracellular molecular chaperones in the folding of oxidized proteins Refolding of colloidal thyroglobulin by protein disulfide isomerase and immunoglobulin heavy chain-binding protein" J Biol Chem 276 24: 21337–42 doi:101074/jbcM101086200 PMID 11294872 
    11. ^ Delom F, Lejeune PJ, Vinet L, Carayon P, Mallet B February 1999 "Involvement of oxidative reactions and extracellular protein chaperones in the rescue of misassembled thyroglobulin in the follicular lumen" Biochem Biophys Res Commun 255 2: 438–43 doi:101006/bbrc19990229 PMID 10049727 

    Further reading

    • Mazzaferri EL, Robbins RJ, Spencer CA, Braverman LE, Pacini F, Wartofsky L, Haugen BR, Sherman SI, Cooper DS, Braunstein GD, Lee S, Davies TF, Arafah BM, Ladenson PW, Pinchera A 2003 "A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma" J Clin Endocrinol Metab 88 4: 1433–41 doi:101210/jc2002-021702 PMID 12679418 
    • Henry M, Zanelli E, Piechaczyk M, Pau B, Malthièry Y 1992 "A major human thyroglobulin epitope defined with monoclonal antibodies is mainly recognized by human autoantibodies" Eur J Immunol 22 2: 315–9 doi:101002/eji1830220205 PMID 1371467 
    • Targovnik HM, Cochaux P, Corach D, Vassart G 1992 "Identification of a minor Tg mRNA transcript in RNA from normal and goitrous thyroids" Mol Cell Endocrinol 84 1-2: R23–6 doi:101016/0303-72079290087-M PMID 1639210 
    • Dunn AD, Crutchfield HE, Dunn JT 1991 "Thyroglobulin processing by thyroidal proteases Major sites of cleavage by cathepsins B, D, and L" J Biol Chem 266 30: 20198–204 PMID 1939080 
    • Lamas L, Anderson PC, Fox JW, Dunn JT 1989 "Consensus sequences for early iodination and hormonogenesis in human thyroglobulin" J Biol Chem 264 23: 13541–5 PMID 2760035 
    • Marriq C, Lejeune PJ, Venot N, Vinet L 1989 "Hormone synthesis in human thyroglobulin: possible cleavage of the polypeptide chain at the tyrosine donor site" FEBS Lett 242 2: 414–8 doi:101016/0014-57938980513-7 PMID 2914619 
    • Christophe D, Cabrer B, Bacolla A, Targovnik H, Pohl V, Vassart G 1985 "An unusually long polypurine-polypyrimidine sequence is located upstream from the human thyroglobulin gene" Nucleic Acids Res 13 14: 5127–44 doi:101093/nar/13145127 PMC 321854  PMID 2991855 
    • Baas F, van Ommen GJ, Bikker H, Arnberg AC, de Vijlder JJ 1986 "The human thyroglobulin gene is over 300 kb long and contains introns of up to 64 kb" Nucleic Acids Res 14 13: 5171–86 doi:101093/nar/14135171 PMC 311533  PMID 3016640 
    • Kubak BM, Potempa LA, Anderson B, Mahklouf S, Venegas M, Gewurz H, Gewurz AT 1989 "Evidence that serum amyloid P component binds to mannose-terminated sequences of polysaccharides and glycoproteins" Mol Immunol 25 9: 851–8 doi:101016/0161-58908890121-6 PMID 3211159 
    • Malthiéry Y, Lissitzky S 1987 "Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA" Eur J Biochem 165 3: 491–8 doi:101111/j1432-10331987tb11466x PMID 3595599 
    • Parma J, Christophe D, Pohl V, Vassart G 1988 "Structural organization of the 5' region of the thyroglobulin gene Evidence for intron loss and "exonization" during evolution" J Mol Biol 196 4: 769–79 doi:101016/0022-28368790403-7 PMID 3681978 
    • Bergé-Lefranc JL, Cartouzou G, Mattéi MG, Passage E, Malezet-Desmoulins C, Lissitzky S 1985 "Localization of the thyroglobulin gene by in situ hybridization to human chromosomes" Hum Genet 69 1: 28–31 doi:101007/BF00295525 PMID 3967888 
    • Malthiéry Y, Lissitzky S 1985 "Sequence of the 5'-end quarter of the human-thyroglobulin messenger ribonucleic acid and of its deduced amino-acid sequence" Eur J Biochem 147 1: 53–8 doi:101111/j1432-10331985tb08717x PMID 3971976 
    • Avvedimento VE, Di Lauro R, Monticelli A, Bernardi F, Patracchini P, Calzolari E, Martini G, Varrone S 1985 "Mapping of human thyroglobulin gene on the long arm of chromosome 8 by in situ hybridization" Hum Genet 71 2: 163–6 doi:101007/BF00283375 PMID 4043966 
    • Xiao S, Pollock HG, Taurog A, Rawitch AB 1995 "Characterization of hormonogenic sites in an N-terminal, cyanogen bromide fragment of human thyroglobulin" Arch Biochem Biophys 320 1: 96–105 doi:101006/abbi19951346 PMID 7793989 
    • Corral J, Martín C, Pérez R, Sánchez I, Mories MT, San Millan JL, Miralles JM, González-Sarmiento R 1993 "Thyroglobulin gene point mutation associated with non-endemic simple goitre" Lancet 341 8843: 462–4 doi:101016/0140-67369390209-Y PMID 8094490 
    • Gentile F, Salvatore G 1994 "Preferential sites of proteolytic cleavage of bovine, human and rat thyroglobulin The use of limited proteolysis to detect solvent-exposed regions of the primary structure" Eur J Biochem 218 2: 603–21 doi:101111/j1432-10331993tb18414x PMID 8269951 
    • Mallet B, Lejeune PJ, Baudry N, Niccoli P, Carayon P, Franc JL 1996 "N-glycans modulate in vivo and in vitro thyroid hormone synthesis Study at the N-terminal domain of thyroglobulin" J Biol Chem 270 50: 29881–8 doi:101074/jbc2705029881 PMID 8530385 
    • Yang SX, Pollock HG, Rawitch AB 1996 "Glycosylation in human thyroglobulin: location of the N-linked oligosaccharide units and comparison with bovine thyroglobulin" Arch Biochem Biophys 327 1: 61–70 doi:101006/abbi19960093 PMID 8615697 
    • Molina F, Bouanani M, Pau B, Granier C 1996 "Characterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families" Eur J Biochem 240 1: 125–33 doi:101111/j1432-103319960125hx PMID 8797845 
    • Grani G, Fumarola A Jun 2014 "Thyroglobulin in Lymph Node Fine-Needle Aspiration Washout: A Systematic Review and Meta-analysis of Diagnostic Accuracy" The Journal of Clinical Endocrinology and Metabolism 99 6: 1970–82 doi:101210/jc2014-1098 PMID 24617715 

    External links

    • Thyroglobulin - Lab Tests Online
    • Histology at KUMC endo-endo11
    • Overview at colostateedu
    • Histology image: 14302loa – Histology Learning System at Boston University

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    Thyroglobulin


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      Thyroglobulin beatiful post thanks!

      29.10.2014


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