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== Synthesis <ref> https://doi.org/10.1016/0022-2836(87)90403-7</ref><ref>DOI 11581009</ref> <ref> https://doi.org/10.1111/j.1432-1033.1987.tb11466.x</ref><ref>DOI 11479128</ref><ref> https://doi.org/10.1016/0014-5793(82)80346-3</ref><ref>DOI 3016640</ref> ==
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== Synthesis <ref>PMID: 3681978</ref><ref>DOI 11581009</ref> <ref>PMID: 3595599</ref><ref>DOI 11479128</ref><ref>PMID: 6895876</ref><ref>DOI 3016640</ref> ==
=== Role and composition of the thyroid gland ===
=== Role and composition of the thyroid gland ===
The thyroid gland is an endocrine organ located in the neck that secretes thyroid hormones into the bloodstream. Among them, T4 and T3 are involved in the growth, development and regulation of the metabolism of vertebrates.
The thyroid gland is an endocrine organ located in the neck that secretes thyroid hormones into the bloodstream. Among them, T4 and T3 are involved in the growth, development and regulation of the metabolism of vertebrates.
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Once iodization and coupling have been performed, endocytosis of the colloid to the lysosome occurs. The <scene name='86/868183/Full_tg/2'>TG</scene> is proteolyzed by cathepsin proteases<ref>DOI 1939080</ref> and 7 TH are thus released from 14 mono- or di iodinated tyrosines.
Once iodization and coupling have been performed, endocytosis of the colloid to the lysosome occurs. The <scene name='86/868183/Full_tg/2'>TG</scene> is proteolyzed by cathepsin proteases<ref>DOI 1939080</ref> and 7 TH are thus released from 14 mono- or di iodinated tyrosines.
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The hormone synthesis function of TG is thus particularly linked to its structure. Moreover, research shows that denaturation or a simple modification of its conformation prevents the formation of TH <ref>DOI 10.1016/0005-2795(73)90365-6</ref><ref>DOI 456595</ref>.
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The hormone synthesis function of TG is thus particularly linked to its structure. Moreover, research shows that denaturation or a simple modification of its conformation prevents the formation of TH <ref>PMID:4710237</ref><ref>DOI 456595</ref>.
==== Control ====
==== Control ====
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The synthesis of TH from TG is stimulated by thyroid stimulating hormone (TSH) secreted by the pituitary gland, a gland of the brain. When the TSH receptor is activated, glycosylations leading to the mono iodination of tyrosines promote the synthesis of T3<ref>DOI 3182849</ref><ref>DI 10.1016/S0021-9258(18)46037-1</ref>.
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The synthesis of TH from TG is stimulated by thyroid stimulating hormone (TSH) secreted by the pituitary gland, a gland of the brain. When the TSH receptor is activated, glycosylations leading to the mono iodination of tyrosines promote the synthesis of T3<ref>DOI 3182849</ref><ref>PMID: 1370485</ref>.
On the other hand, if the amount of hormones is too high, a negative feedback is exerted on this process while a small amount of these hormones exerts a positive feedback.
On the other hand, if the amount of hormones is too high, a negative feedback is exerted on this process while a small amount of these hormones exerts a positive feedback.
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The complex and particularly stable structure of <scene name='86/868183/Full_tg/2'>TG</scene> gives it iodide reservoir properties. Indeed, all iodinated but non-hormonoid tyrosines are useful for iodine storage in the thyroid gland.
The complex and particularly stable structure of <scene name='86/868183/Full_tg/2'>TG</scene> gives it iodide reservoir properties. Indeed, all iodinated but non-hormonoid tyrosines are useful for iodine storage in the thyroid gland.
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== Interest in the medical field<ref>DOI 17614775</ref><ref>DOI 12721190</ref><ref>DOI 24147207</ref><ref>DOI 11788684</ref><ref>DOI 17201802</ref><ref>DOI 10.1677/ERC-10-0292</ref><ref>DOI 5773064</ref><ref>DOI 3681445</ref><ref>DOI 12089177</ref><ref>DOI 21134539</ref><ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref>DOI 21649472</ref><ref>DOI 28593684</ref><ref>DOI 29246752</ref><ref>DOI : 10.1001/jama.1979.03290350043022</ref> ==
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== Interest in the medical field<ref>DOI 17614775</ref><ref>DOI 12721190</ref><ref>DOI 24147207</ref><ref>DOI 11788684</ref><ref>DOI 17201802</ref><ref>DOI 10.1677/ERC-10-0292</ref><ref>DOI 5773064</ref><ref>DOI 3681445</ref><ref>DOI 12089177</ref><ref>DOI 21134539</ref><ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref>DOI 21649472</ref><ref>DOI 28593684</ref><ref>DOI 29246752</ref><ref>PMID: 762873</ref><ref>DOI 26595189</ref> ==
=== Modification of the TG quantity related to the desease ===
=== Modification of the TG quantity related to the desease ===
A healthy subject has between 5 and 25 µg of TG per liter of blood. In case of thyroid dysfunction, this level may increase or decrease. For example, it decreases in the case of congenital athyreosis (insufficiency of the thyroid gland) or prior to a miscarriage due to the presence of anti-TG antibodies, but increases in the case of cancer, thyroiditis, inflammation of the thyroid or autoimmune thyroid diseases AITD (Grave's disease, Hashimoto's thyroiditis).
A healthy subject has between 5 and 25 µg of TG per liter of blood. In case of thyroid dysfunction, this level may increase or decrease. For example, it decreases in the case of congenital athyreosis (insufficiency of the thyroid gland) or prior to a miscarriage due to the presence of anti-TG antibodies, but increases in the case of cancer, thyroiditis, inflammation of the thyroid or autoimmune thyroid diseases AITD (Grave's disease, Hashimoto's thyroiditis).
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== References ==
== References ==
<references/>
<references/>
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<ref>DOI 26595189</ref>
 

Revision as of 08:51, 8 January 2022

This Sandbox is Reserved from 26/11/2020, through 26/11/2021 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1643 through Sandbox Reserved 1664.
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Human thyroglobulin (TG)

Human thyroglobulin

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References

  1. ↑ Parma J, Christophe D, Pohl V, Vassart G. Structural organization of the 5' region of the thyroglobulin gene. Evidence for intron loss and "exonization" during evolution. J Mol Biol. 1987 Aug 20;196(4):769-79. PMID:3681978
  2. ↑ Mendive FM, Rivolta CM, Moya CM, Vassart G, Targovnik HM. Genomic organization of the human thyroglobulin gene: the complete intron-exon structure. Eur J Endocrinol. 2001 Oct;145(4):485-96. doi: 10.1530/eje.0.1450485. PMID:11581009 doi:http://dx.doi.org/10.1530/eje.0.1450485
  3. ↑ Malthiery Y, Lissitzky S. Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA. Eur J Biochem. 1987 Jun 15;165(3):491-8. PMID:3595599
  4. ↑ 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 Aug;170(2):307-21. doi: 10.1677/joe.0.1700307. PMID:11479128 doi:http://dx.doi.org/10.1677/joe.0.1700307
  5. ↑ Brocas H, Christophe D, Pohl V, Vassart G. Cloning of human thyroglobulin complementary DNA. FEBS Lett. 1982 Jan 25;137(2):189-92. doi: 10.1016/0014-5793(82)80346-3. PMID:6895876 doi:http://dx.doi.org/10.1016/0014-5793(82)80346-3
  6. ↑ Baas F, van Ommen GJ, Bikker H, Arnberg AC, de Vijlder JJ. The human thyroglobulin gene is over 300 kb long and contains introns of up to 64 kb. Nucleic Acids Res. 1986 Jul 11;14(13):5171-86. doi: 10.1093/nar/14.13.5171. PMID:3016640 doi:http://dx.doi.org/10.1093/nar/14.13.5171
  7. ↑ Coscia F, Taler-Vercic A, Chang VT, Sinn L, O'Reilly FJ, Izore T, Renko M, Berger I, Rappsilber J, Turk D, Lowe J. The structure of human thyroglobulin. Nature. 2020 Feb 5. pii: 10.1038/s41586-020-1995-4. doi:, 10.1038/s41586-020-1995-4. PMID:32025030 doi:http://dx.doi.org/10.1038/s41586-020-1995-4
  8. ↑ Di Jeso B, Ulianich L, Pacifico F, Leonardi A, Vito P, Consiglio E, Formisano S, Arvan P. Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. Biochem J. 2003 Mar 1;370(Pt 2):449-58. doi: 10.1042/BJ20021257. PMID:12401114 doi:http://dx.doi.org/10.1042/BJ20021257
  9. ↑ de Vijlder JJ, den Hartog MT. Anionic iodotyrosine residues are required for iodothyronine synthesis. Eur J Endocrinol. 1998 Feb;138(2):227-31. doi: 10.1530/eje.0.1380227. PMID:9506870 doi:http://dx.doi.org/10.1530/eje.0.1380227
  10. ↑ Dunn AD, Crutchfield HE, Dunn JT. Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L. J Biol Chem. 1991 Oct 25;266(30):20198-204. PMID:1939080
  11. ↑ Rolland M, Montfort MF, Lissitzky S. Efficiency of thyroglobulin as a thyroid hormone-forming protein. Biochim Biophys Acta. 1973 Apr 20;303(2):338-47. doi:, 10.1016/0005-2795(73)90365-6. PMID:4710237 doi:http://dx.doi.org/10.1016/0005-2795(73)90365-6
  12. ↑ Maurizis JC, Marriq C, Michelot J, Rolland M, Lissitzky S. Thyroid peroxidase-induced thyroid hormone synthesis in relation to thyroglobulin structure. FEBS Lett. 1979 Jun 1;102(1):82-6. doi: 10.1016/0014-5793(79)80933-3. PMID:456595 doi:http://dx.doi.org/10.1016/0014-5793(79)80933-3
  13. ↑ Fassler CA, Dunn JT, Anderson PC, Fox JW, Dunn AD, Hite LA, Moore RC, Kim PS. Thyrotropin alters the utilization of thyroglobulin's hormonogenic sites. J Biol Chem. 1988 Nov 25;263(33):17366-71. PMID:3182849
  14. ↑ Di Jeso B, Liguoro D, Ferranti P, Marinaccio M, Acquaviva R, Formisano S, Consiglio E. Modulation of the carbohydrate moiety of thyroglobulin by thyrotropin and calcium in Fisher rat thyroid line-5 cells. J Biol Chem. 1992 Jan 25;267(3):1938-44. PMID:1370485
  15. ↑ Leboeuf R, Emerick LE, Martorella AJ, Tuttle RM. Impact of pregnancy on serum thyroglobulin and detection of recurrent disease shortly after delivery in thyroid cancer survivors. Thyroid. 2007 Jun;17(6):543-7. doi: 10.1089/thy.2007.0020. PMID:17614775 doi:http://dx.doi.org/10.1089/thy.2007.0020
  16. ↑ Matalon ST, Blank M, Levy Y, Carp HJ, Arad A, Burek L, Grunebaum E, Sherer Y, Ornoy A, Refetoff S, Weiss RE, Rose NR, Shoenfeld Y. The pathogenic role of anti-thyroglobulin antibody on pregnancy: evidence from an active immunization model in mice. Hum Reprod. 2003 May;18(5):1094-9. doi: 10.1093/humrep/deg210. PMID:12721190 doi:http://dx.doi.org/10.1093/humrep/deg210
  17. ↑ Kawasaki E, Yasui J, Tsurumaru M, Takashima H, Ikeoka T, Mori F, Akazawa S, Ueki I, Kobayashi M, Kuwahara H, Abiru N, Yamasaki H, Kawakami A. Sequential elevation of autoantibodies to thyroglobulin and glutamic acid decarboxylase in type 1 diabetes. World J Diabetes. 2013 Oct 15;4(5):227-30. doi: 10.4239/wjd.v4.i5.227. PMID:24147207 doi:http://dx.doi.org/10.4239/wjd.v4.i5.227
  18. ↑ Tomer Y, Greenberg DA, Concepcion E, Ban Y, Davies TF. Thyroglobulin is a thyroid specific gene for the familial autoimmune thyroid diseases. J Clin Endocrinol Metab. 2002 Jan;87(1):404-7. doi: 10.1210/jcem.87.1.8291. PMID:11788684 doi:http://dx.doi.org/10.1210/jcem.87.1.8291
  19. ↑ Heemstra KA, Liu YY, Stokkel M, Kievit J, Corssmit E, Pereira AM, Romijn JA, Smit JW. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2007 Jan;66(1):58-64. doi:, 10.1111/j.1365-2265.2006.02685.x. PMID:17201802 doi:http://dx.doi.org/10.1111/j.1365-2265.2006.02685.x
  20. ↑ Nascimento C, Borget I, Al Ghuzlan A, Deandreis D, Chami L, Travagli JP, Hartl D, Lumbroso J, Chougnet C, Lacroix L, Baudin E, Schlumberger M, Leboulleux S. Persistent disease and recurrence in differentiated thyroid cancer patients with undetectable postoperative stimulated thyroglobulin level. Endocr Relat Cancer. 2011 Mar 3;18(2):R29-40. doi: 10.1677/ERC-10-0292. Print, 2011 Apr. PMID:21183629 doi:http://dx.doi.org/10.1677/ERC-10-0292
  21. ↑ Torrigiani G, Doniach D, Roitt IM. Serum thyroglobulin levels in healthy subjects and in patients with thyroid disease. J Clin Endocrinol Metab. 1969 Mar;29(3):305-14. doi: 10.1210/jcem-29-3-305. PMID:5773064 doi:http://dx.doi.org/10.1210/jcem-29-3-305
  22. ↑ Pacini F, Lippi F, Formica N, Elisei R, Anelli S, Ceccarelli C, Pinchera A. Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels. J Nucl Med. 1987 Dec;28(12):1888-91. PMID:3681445
  23. ↑ Morgenthaler NG, Froehlich J, Rendl J, Willnich M, Alonso C, Bergmann A, Reiners C. Technical evaluation of a new immunoradiometric and a new immunoluminometric assay for thyroglobulin. Clin Chem. 2002 Jul;48(7):1077-83. PMID:12089177
  24. ↑ Hughes DT, White ML, Miller BS, Gauger PG, Burney RE, Doherty GM. Influence of prophylactic central lymph node dissection on postoperative thyroglobulin levels and radioiodine treatment in papillary thyroid cancer. Surgery. 2010 Dec;148(6):1100-6; discussion 1006-7. doi:, 10.1016/j.surg.2010.09.019. PMID:21134539 doi:http://dx.doi.org/10.1016/j.surg.2010.09.019
  25. ↑ Galligan JP, Winship J, van Doorn T, Mortimer RH. A comparison of serum thyroglobulin measurements and whole body 131I scanning in the management of treated differentiated thyroid carcinoma. Aust N Z J Med. 1982 Aug;12(4):248-54. doi: 10.1111/j.1445-5994.1982.tb03805.x. PMID:6814409 doi:http://dx.doi.org/10.1111/j.1445-5994.1982.tb03805.x
  26. ↑ Flores-Rebollar A, Perez-Diaz I, Lagunas-Barcenas S, Garcia-Martinez B, Rivera-Moscoso R, Fagundo-Sierra R. Clinical utility of an ultrasensitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer: can the stimulation test be avoided in patients with an intermediate recurrence risk? Acta Otorhinolaryngol Ital. 2018 Jun;38(3):188-193. doi: 10.14639/0392-100X-1494. PMID:29984794 doi:http://dx.doi.org/10.14639/0392-100X-1494
  27. ↑ Miyauchi A, Kudo T, Miya A, Kobayashi K, Ito Y, Takamura Y, Higashiyama T, Fukushima M, Kihara M, Inoue H, Tomoda C, Yabuta T, Masuoka H. Prognostic impact of serum thyroglobulin doubling-time under thyrotropin suppression in patients with papillary thyroid carcinoma who underwent total thyroidectomy. Thyroid. 2011 Jul;21(7):707-16. doi: 10.1089/thy.2010.0355. Epub 2011 Jun 7. PMID:21649472 doi:http://dx.doi.org/10.1089/thy.2010.0355
  28. ↑ Katko M, Gazso AA, Hircsu I, Bhattoa HP, Molnar Z, Kovacs B, Andrasi D, Aranyosi J, Makai R, Veress L, Torok O, Bodor M, Samson L, Nagy EV. Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply. Matern Child Nutr. 2018 Jan;14(1). doi: 10.1111/mcn.12470. Epub 2017 Jun 7. PMID:28593684 doi:http://dx.doi.org/10.1111/mcn.12470
  29. ↑ De Leo S, Pearce EN. Autoimmune thyroid disease during pregnancy. Lancet Diabetes Endocrinol. 2018 Jul;6(7):575-586. doi:, 10.1016/S2213-8587(17)30402-3. Epub 2017 Dec 12. PMID:29246752 doi:http://dx.doi.org/10.1016/S2213-8587(17)30402-3
  30. ↑ Gerfo PL, Colacchio T, Colacchio D, Feind C. Thyroglobulin in benign and malignant thyroid disease. JAMA. 1979 Mar 2;241(9):923-4. PMID:762873
  31. ↑ Di Jeso B, Arvan P. Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology. Endocr Rev. 2016 Feb;37(1):2-36. doi: 10.1210/er.2015-1090. Epub 2015 Nov 23. PMID:26595189 doi:http://dx.doi.org/10.1210/er.2015-1090
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