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.
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.
↑Farid NR, Szkudlinski MW (Sep 2004). "Minireview: structural and functional evolution of the thyrotropin receptor". Endocrinology. 145 (9): 4048–57. doi:10.1210/en.2004-0437. PMID15231707.
↑Calebiro D, Nikolaev VO, Lohse MJ (Jul 2010). "Imaging of persistent cAMP signaling by internalized G protein-coupled receptors". Journal of Molecular Endocrinology. 45 (1): 1–8. doi:10.1677/JME-10-0014. PMID20378719.
Further reading
Führer D, Wonerow P, Willgerodt H, Paschke R (Dec 1997). "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. doi:10.1210/jc.82.12.4234. PMID9398746.
Farid NR, Kascur V, Balazs C (Jul 2000). "The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations". European Journal of Endocrinology / European Federation of Endocrine Societies. 143 (1): 25–30. doi:10.1530/eje.0.1430025. PMID10870027.
Tonacchera M, Vitti P, De Servi M, Agretti P, De Marco G, Chiovato L, Pinchera A (2004). "Gain of function TSH receptor mutations and iodine deficiency: implications in iodine prophylaxis". Journal of Endocrinological Investigation. 26 (2 Suppl): 2–6. PMID12762632.
Arturi F, Scarpelli D, Coco A, Sacco R, Bruno R, Filetti S, Russo D (Apr 2003). "Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years after their first discovery: unresolved questions". Thyroid. 13 (4): 341–3. doi:10.1089/105072503321669811. PMID12804102.
Vaidya B, Campbell V, Tripp JH, Spyer G, Hattersley AT, Ellard S (Jun 2004). "Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation". Clinical Endocrinology. 60 (6): 711–8. doi:10.1111/j.1365-2265.2004.02040.x. PMID15163335.
Takeshita A, Nagayama Y, Fujiyama K, Yokoyama N, Namba H, Yamashita S, Izumi M, Nagataki S (Nov 1992). "Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript". Biochemical and Biophysical Research Communications. 188 (3): 1214–9. doi:10.1016/0006-291X(92)91360-3. PMID1445355.
Graves PN, Tomer Y, Davies TF (Sep 1992). "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. doi:10.1016/0006-291X(92)91315-H. PMID1530609.
Nagayama Y, Russo D, Wadsworth HL, Chazenbalk GD, Rapoport B (Aug 1991). "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. PMID1651314.
Murakami M, Mori M (Aug 1990). "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. doi:10.1016/0006-291X(90)91423-P. PMID1697467.
Heldin NE, Gustavsson B, Westermark K, Westermark B (Dec 1991). "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. doi:10.1210/jcem-73-6-1374. PMID1955520.
Libert F, Passage E, Lefort A, Vassart G, Mattei MG (1991). "Localization of human thyrotropin receptor gene to chromosome region 14q3 by in situ hybridization". Cytogenetics and Cell Genetics. 54 (1–2): 82–3. doi:10.1159/000132964. PMID2249482.
Frazier AL, Robbins LS, Stork PJ, Sprengel R, Segaloff DL, Cone RD (Aug 1990). "Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing". Molecular Endocrinology. 4 (8): 1264–76. doi:10.1210/mend-4-8-1264. PMID2293030.
Misrahi M, Loosfelt H, Atger M, Sar S, Guiochon-Mantel A, Milgrom E (Jan 1990). "Cloning, sequencing and expression of human TSH receptor". Biochemical and Biophysical Research Communications. 166 (1): 394–403. doi:10.1016/0006-291X(90)91958-U. PMID2302212.
Nagayama Y, Kaufman KD, Seto P, Rapoport B (Dec 1989). "Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor". Biochemical and Biophysical Research Communications. 165 (3): 1184–90. doi:10.1016/0006-291X(89)92727-7. PMID2558651.
Libert F, Lefort A, Gerard C, Parmentier M, Perret J, Ludgate M, Dumont JE, Vassart G (Dec 1989). "Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies". Biochemical and Biophysical Research Communications. 165 (3): 1250–5. doi:10.1016/0006-291X(89)92736-8. PMID2610690.
Cuddihy RM, Bryant WP, Bahn RS (Aug 1995). "Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor". Thyroid. 5 (4): 255–7. doi:10.1089/thy.1995.5.255. PMID7488864.
Bahn RS, Dutton CM, Heufelder AE, Sarkar G (Feb 1994). "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. doi:10.1210/jc.78.2.256. PMID7508946.
Sunthornthepvarakui T, Gottschalk ME, Hayashi Y, Refetoff S (Jan 1995). "Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene". The New England Journal of Medicine. 332 (3): 155–60. doi:10.1056/NEJM199501193320305. PMID7528344.