Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Thyrotropin Receptor

  • Samer El-Kaissi
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101925

Synonyms

Historical Background

The thyrotropin receptor (TSHR) is a seven-transmembrane protein that belongs to the family of G-protein-coupled receptors (GPCR). The receptor is located on the surface of thyroid follicular cells, and its activation leads to thyroid hormone production and growth and proliferation of thyrocytes.

The primary activator of the TSHR is the thyroid-stimulating hormone (TSH) or thyrotropin, although the receptor may also be activated by stimulating antibodies as occurs in autoimmune hyperthyroidism, known as Graves’ disease. The TSHR is expressed in many non-thyroidal tissues and may be involved in the systemic manifestations of thyroid disease, such as thyroid-associated ophthalmopathy, pretibial myxedema, and metabolic bone disease.

Structurally, the TSHR can...

This is a preview of subscription content, log in to check access.

References

  1. Aliyev A, Patel J, Brainard J, Gupta M, Nasr C, Hatipoglu B, et al. Diagnostic accuracy of circulating thyrotropin receptor messenger RNA combined with neck ultrasonography in patients with Bethesda III-V thyroid cytology. Surgery. 2016;159:113–7. doi:10.1016/j.surg.2015.06.063.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Allen MD, Neumann S, Gershengorn MC. Small-molecule thyrotropin receptor agonist activates naturally occurring thyrotropin-insensitive mutants and reveals their distinct cyclic adenosine monophosphate signal persistence. Thyroid. 2011;21:907–12. doi:10.1089/thy.2011.0025.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Allgeier A, Offermanns S, Van Sande J, Spicher K, Schultz G, Dumont JE. The human thyrotropin receptor activates G-proteins Gs and Gq/11. J Biol Chem. 1994;269:13733–5.PubMedPubMedCentralGoogle Scholar
  4. Chen CR, Chazenbalk GD, Wawrowsky KA, McLachlan SM, Rapoport B. Evidence that human thyroid cells express uncleaved, single-chain thyrotropin receptors on their surface. Endocrinology. 2006;147:3107–13. doi:10.1210/en.2005-1514.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Coulon AL, Savagner F, Briet C, Vernin M, Munier M, Chabre O, et al. Prolonged and severe gestational thyrotoxicosis due to enhanced hCG sensitivity of a mutant thyrotropin receptor. J Clin Endocrinol Metab. 2016;101:10–1. doi:10.1210/jc.2015-3670.CrossRefPubMedPubMedCentralGoogle Scholar
  6. El-Kaissi S, Wall JR. Targeting the thyrotropin receptor in thyroid disease. Expert Opin Ther Targets. 2012;16:719–27. doi:10.1517/14728222.2012.692779.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Emerson CH. When will thyrotropin receptor antagonists and inverse thyrotropin receptor agonists become available for clinical use? Thyroid. 2011;21:817–9. doi:10.1089/thy.2011.2108.ed.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Gozu HI, Lublinghoff J, Bircan R, Paschke R. Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism. Mol Cell Endocrinol. 2010;322:125–34. doi:10.1016/j.mce.2010.02.001.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Kleinau G, Krause G. Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr Rev. 2009;30:133–51. doi:10.1210/er.2008-0044.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Kopp P. The TSH receptor and its role in thyroid disease. Cell Mol Life Sci. 2001;58:1301–22.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Latif R, Ando T, Davies TF. Monomerization as a prerequisite for intramolecular cleavage and shedding of the thyrotropin receptor. Endocrinology. 2004;145:5580–8. doi:10.1210/en.2004-0797.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Latif R, Morshed SA, Zaidi M, Davies TF. The thyroid-stimulating hormone receptor: impact of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on multimerization, cleavage, and signaling. Endocrinol Metab Clin N Am. 2009;38:319–41. doi:10.1016/j.ecl.2009.01.006.CrossRefGoogle Scholar
  13. Morgan SJ, Neumann S, Marcus-Samuels B, Gershengorn MC. Thyrotropin and Insulin-Like Growth Factor 1 receptor crosstalk upregulates sodium-iodide symporter expression in primary cultures of human thyrocytes. Thyroid. 2016. doi:10.1089/thy.2016.0323.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Nishihara E, Fukata S, Hishinuma A, Amino N, Miyauchi A. Prevalence of thyrotropin receptor germline mutations and clinical courses in 89 hyperthyroid patients with diffuse goiter and negative anti-thyrotropin receptor antibodies. Thyroid. 2014;24:789–95. doi:10.1089/thy.2013.0431.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Parmentier M, Libert F, Maenhaut C, Lefort A, Gerard C, Perret J, et al. Molecular cloning of the thyrotropin receptor. Science. 1989;246:1620–2.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Persani L, Calebiro D, Cordella D, Weber G, Gelmini G, Libri D, et al. Genetics and phenomics of hypothyroidism due to TSH resistance. Mol Cell Endocrinol. 2010;322:72–82. doi:10.1016/j.mce.2010.01.008.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev. 1998;19:673–716. doi:10.1210/edrv.19.6.0352.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Tenenbaum-Rakover Y, Almashanu S, Hess O, Admoni O, Hag-Dahood Mahameed A, Schwartz N, et al. Long-term outcome of loss-of-function mutations in thyrotropin receptor gene. Thyroid. 2015;25:292–9. doi:10.1089/thy.2014.0311.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Vassart G, Costagliola S. A physiological role for the posttranslational cleavage of the thyrotropin receptor? Endocrinology. 2004;145:1–3. doi:10.1210/en.2003-1225.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Weetman AP. Graves’ disease. N Engl J Med. 2000;343:1236–48. doi:10.1056/NEJM200010263431707.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Medical Subspecialties InstituteCleveland Clinic Abu DhabiAbu DhabiUAE