Thyroglobulin

Thyroglobulin (Tg) is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as "colloid".

Thyroglobulin should not be confused with Thyroxine-binding globulin, a carrier protein responsible for carrying the thyroid hormones in the blood.

Function

Tg is used by the thyroid gland to produce the thyroid hormones thyroxine (T4) and triiodothyronine (T3). The active form of thyroxine, triiodothyronine, is produced both within the thyroid gland and periphery by 5'-deiodinase (which has been referred to as tetraiodothyronine 5' deiodinase.)

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.

Proteases in lysosomes digest iodinated thyroglobulin, releasing T3 and T4. [GeorgiaPhysiology|5/5ch5/s5ch5_6]

Clinical significance

Patients with Hashimoto's thyroiditis or Graves' disease, frequently develop antibodies against Tg. Tg-specific antibodies help in the diagnosis of these diseases, but they also may be present in apparently healthy euthyroid individuals.

Thyroglobulin levels in the blood can be used as a tumor marker for certain kinds of thyroid cancer. Thyroglobulin levels in the blood can also be elevated in cases of Graves' disease.

References

Further reading

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citations =
*cite journal | author=Mazzaferri EL, Robbins RJ, Spencer CA, "et al." |title=A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma |journal=J. Clin. Endocrinol. Metab. |volume=88 |issue= 4 |pages= 1433–41 |year= 2003 |pmid= 12679418 |doi=
*cite journal | author=Henry M, Zanelli E, Piechaczyk M, "et al." |title=A major human thyroglobulin epitope defined with monoclonal antibodies is mainly recognized by human autoantibodies |journal=Eur. J. Immunol. |volume=22 |issue= 2 |pages= 315–9 |year= 1992 |pmid= 1371467| doi=10.1002/eji.1830220205
*cite journal | author=Targovnik HM, Cochaux P, Corach D, Vassart G |title=Identification of a minor Tg mRNA transcript in RNA from normal and goitrous thyroids |journal=Mol. Cell. Endocrinol. |volume=84 |issue= 1-2 |pages= R23–6 |year= 1992 |pmid= 1639210| doi=10.1016/0303-7207(92)90087-M
*cite journal | author=Dunn AD, Crutchfield HE, Dunn JT |title=Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L |journal=J. Biol. Chem. |volume=266 |issue= 30 |pages= 20198–204 |year= 1991 |pmid= 1939080 |doi=
*cite journal | author=Lamas L, Anderson PC, Fox JW, Dunn JT |title=Consensus sequences for early iodination and hormonogenesis in human thyroglobulin |journal=J. Biol. Chem. |volume=264 |issue= 23 |pages= 13541–5 |year= 1989 |pmid= 2760035 |doi=
*cite journal | author=Marriq C, Lejeune PJ, Venot N, Vinet L |title=Hormone synthesis in human thyroglobulin: possible cleavage of the polypeptide chain at the tyrosine donor site |journal=FEBS Lett. |volume=242 |issue= 2 |pages= 414–8 |year= 1989 |pmid= 2914619| doi=10.1016/0014-5793(89)80513-7
*cite journal | author=Christophe D, Cabrer B, Bacolla A, "et al." |title=An unusually long poly(purine)-poly(pyrimidine) sequence is located upstream from the human thyroglobulin gene |journal=Nucleic Acids Res. |volume=13 |issue= 14 |pages= 5127–44 |year= 1985 |pmid= 2991855| doi=10.1093/nar/13.14.5127
*cite journal | author=Baas F, van Ommen GJ, Bikker H, "et al." |title=The human thyroglobulin gene is over 300 kb long and contains introns of up to 64 kb |journal=Nucleic Acids Res. |volume=14 |issue= 13 |pages= 5171–86 |year= 1986 |pmid= 3016640| doi=10.1093/nar/14.13.5171
*cite journal | author=Kubak BM, Potempa LA, Anderson B, "et al." |title=Evidence that serum amyloid P component binds to mannose-terminated sequences of polysaccharides and glycoproteins |journal=Mol. Immunol. |volume=25 |issue= 9 |pages= 851–8 |year= 1989 |pmid= 3211159 |doi=
*cite journal | author=Malthiéry Y, Lissitzky S |title=Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA |journal=Eur. J. Biochem. |volume=165 |issue= 3 |pages= 491–8 |year= 1987 |pmid= 3595599| doi=10.1111/j.1432-1033.1987.tb11466.x
*cite journal | author=Parma J, Christophe D, Pohl V, Vassart G |title=Structural organization of the 5' region of the thyroglobulin gene. Evidence for intron loss and "exonization" during evolution |journal=J. Mol. Biol. |volume=196 |issue= 4 |pages= 769–79 |year= 1988 |pmid= 3681978 |doi=
*cite journal | author=Bergé-Lefranc JL, Cartouzou G, Mattéi MG, "et al." |title=Localization of the thyroglobulin gene by in situ hybridization to human chromosomes |journal=Hum. Genet. |volume=69 |issue= 1 |pages= 28–31 |year= 1985 |pmid= 3967888| doi=10.1007/BF00295525
*cite journal |author=Malthiéry Y, Lissitzky S |title=Sequence of the 5'-end quarter of the human-thyroglobulin messenger ribonucleic acid and of its deduced amino-acid sequence |journal=Eur. J. Biochem. |volume=147 |issue= 1 |pages= 53–8 |year= 1985 |pmid= 3971976|doi=10.1111/j.1432-1033.1985.tb08717.x
*cite journal | author=Avvedimento VE, Di Lauro R, Monticelli A, "et al." |title=Mapping of human thyroglobulin gene on the long arm of chromosome 8 by in situ hybridization |journal=Hum. Genet. |volume=71 |issue= 2 |pages= 163–6 |year= 1985 |pmid= 4043966| doi=10.1007/BF00283375
*cite journal | author=Xiao S, Pollock HG, Taurog A, Rawitch AB |title=Characterization of hormonogenic sites in an N-terminal, cyanogen bromide fragment of human thyroglobulin |journal=Arch. Biochem. Biophys. |volume=320 |issue= 1 |pages= 96–105 |year= 1995 |pmid= 7793989| doi=10.1006/abbi.1995.1346
*cite journal | author=Corral J, Martín C, Pérez R, "et al." |title=Thyroglobulin gene point mutation associated with non-endemic simple goitre |journal=Lancet |volume=341 |issue= 8843 |pages= 462–4 |year= 1993 |pmid= 8094490| doi=10.1016/0140-6736(93)90209-Y
*cite journal | author=Gentile F, Salvatore G |title=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 |journal=Eur. J. Biochem. |volume=218 |issue= 2 |pages= 603–21 |year= 1994 |pmid= 8269951 |doi=
*cite journal | author=Mallet B, Lejeune PJ, Baudry N, "et al." |title=N-glycans modulate in vivo and in vitro thyroid hormone synthesis. Study at the N-terminal domain of thyroglobulin |journal=J. Biol. Chem. |volume=270 |issue= 50 |pages= 29881–8 |year= 1996 |pmid= 8530385 |doi=
*cite journal | author=Yang SX, Pollock HG, Rawitch AB |title=Glycosylation in human thyroglobulin: location of the N-linked oligosaccharide units and comparison with bovine thyroglobulin |journal=Arch. Biochem. Biophys. |volume=327 |issue= 1 |pages= 61–70 |year= 1996 |pmid= 8615697 |doi= 10.1006/abbi.1996.0093
*cite journal | author=Molina F, Bouanani M, Pau B, Granier C |title=Characterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families |journal=Eur. J. Biochem. |volume=240 |issue= 1 |pages= 125–33 |year= 1996 |pmid= 8797845| doi=10.1111/j.1432-1033.1996.0125h.x

External links

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* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/synthesis.html Overview at colostate.edu]
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