Biology:Thyrotropin receptor

Short description: Mammalian protein found in Homo sapiens

Generic protein structure example

The thyrotropin receptor (or TSH receptor) is a receptor (and associated protein) that responds to thyroid-stimulating hormone (also known as "thyrotropin") and stimulates the production of thyroxine (T4) and triiodothyronine (T3). The TSH receptor is a member of the G protein-coupled receptor superfamily of integral membrane proteins and is coupled to the G_s protein.

It is primarily found on the surface of the thyroid epithelial cells, but also found on adipose tissue and fibroblasts. The latter explains the reason of the myxedema finding during Graves disease. In addition, it has also been found to be expressed in the anterior pituitary gland, hypothalamus and kidneys. Its presence in the anterior pituitary gland may be involved in mediating the paracrine signaling feedback inhibition of thyrotropin along the hypothalamus-pituitary-thyroid axis.

Function

Upon binding circulating TSH, a G-protein signal cascade activates adenylyl cyclase and intracellular levels of cAMP rise. cAMP activates all functional aspects of the thyroid cell, including iodine pumping; thyroglobulin synthesis, iodination, endocytosis, and proteolysis; thyroid peroxidase activity; and hormone release. TSHR is involved in regulating seasonal reproduction in vertebrates.

See also

• Graves' disease

Further reading

• "Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism". The Journal of Clinical Endocrinology and Metabolism 82 (12): 4234–8. Dec 1997. doi:10.1210/jcem.82.12.4405. PMID 9398746. 
• "The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations". European Journal of Endocrinology 143 (1): 25–30. Jul 2000. doi:10.1530/eje.0.1430025. PMID 10870027. 
• "Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships". Physiological Reviews 82 (2): 473–502. Apr 2002. doi:10.1152/physrev.00031.2001. PMID 11917095. 
• "Gain of function TSH receptor mutations and iodine deficiency: implications in iodine prophylaxis". Journal of Endocrinological Investigation 26 (2 Suppl): 2–6. 2004. PMID 12762632. 
• "Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years after their first discovery: unresolved questions". Thyroid 13 (4): 341–3. Apr 2003. doi:10.1089/105072503321669811. PMID 12804102. 
• "Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation". Clinical Endocrinology 60 (6): 711–8. Jun 2004. doi:10.1111/j.1365-2265.2004.02040.x. PMID 15163335. 
• "Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript". Biochemical and Biophysical Research Communications 188 (3): 1214–9. Nov 1992. doi:10.1016/0006-291X(92)91360-3. PMID 1445355. 
• "Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor mRNA lacking the transmembrane domain". Biochemical and Biophysical Research Communications 187 (2): 1135–43. Sep 1992. doi:10.1016/0006-291X(92)91315-H. PMID 1530609. 
• "Two-subunit structure of the human thyrotropin receptor". Proceedings of the National Academy of Sciences of the United States of America 89 (9): 3765–9. May 1992. doi:10.1073/pnas.89.9.3765. PMID 1570295. Bibcode: 1992PNAS...89.3765L. 
• "Eleven amino acids (Lys-201 to Lys-211) and 9 amino acids (Gly-222 to Leu-230) in the human thyrotropin receptor are involved in ligand binding". The Journal of Biological Chemistry 266 (23): 14926–30. Aug 1991. doi:10.1016/S0021-9258(18)98566-2. PMID 1651314. 
• "Identification of immunogenic regions in human thyrotropin receptor for immunoglobulin G of patients with Graves' disease". Biochemical and Biophysical Research Communications 171 (1): 512–8. Aug 1990. doi:10.1016/0006-291X(90)91423-P. PMID 1697467. 
• "A somatic point mutation in a putative ligand binding domain of the TSH receptor in a patient with autoimmune hyperthyroidism". The Journal of Clinical Endocrinology and Metabolism 73 (6): 1374–6. Dec 1991. doi:10.1210/jcem-73-6-1374. PMID 1955520. 
• "Localization of human thyrotropin receptor gene to chromosome region 14q3 by in situ hybridization". Cytogenetics and Cell Genetics 54 (1–2): 82–3. 1991. doi:10.1159/000132964. PMID 2249482. 
• "Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing". Molecular Endocrinology 4 (8): 1264–76. Aug 1990. doi:10.1210/mend-4-8-1264. PMID 2293030. 
• "Cloning, sequencing and expression of human TSH receptor". Biochemical and Biophysical Research Communications 166 (1): 394–403. Jan 1990. doi:10.1016/0006-291X(90)91958-U. PMID 2302212. 
• "Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor". Biochemical and Biophysical Research Communications 165 (3): 1184–90. Dec 1989. doi:10.1016/0006-291X(89)92727-7. PMID 2558651. 
• "Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies". Biochemical and Biophysical Research Communications 165 (3): 1250–5. Dec 1989. doi:10.1016/0006-291X(89)92736-8. PMID 2610690. 
• "Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor". Thyroid 5 (4): 255–7. Aug 1995. doi:10.1089/thy.1995.5.255. PMID 7488864. 
• "A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy". The Journal of Clinical Endocrinology and Metabolism 78 (2): 256–60. Feb 1994. doi:10.1210/jcem.78.2.7508946. PMID 7508946. http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-16001-1. 
• "Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene". The New England Journal of Medicine 332 (3): 155–60. Jan 1995. doi:10.1056/NEJM199501193320305. PMID 7528344. 

External links

• "Glycoprotein Hormone Receptors: TSH". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2988. 
• Thyrotropin+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
• SSFA-GPHR: Sequence Structure Function Analysis of Glycoprotein Hormone Receptors
• GRIS: Glycoprotein-hormone Receptor Information System
• Overview of all the structural information available in the PDB for UniProt: P16473 (Thyrotropin receptor) at the PDBe-KB.