Skip to main content
SpringerLink
Log in

Hypo- and Hyperthyroidism Caused by Mutations of the TSH Receptor

  • Chapter
G Proteins, Receptors, and Disease

Part of the book series: Contemporary Endocrinology ((COE,volume 6))

Abstract

The main function of the thyroid gland is to synthesize, store, and secrete the thyroid hormones T3 and T4. Regulation of this function is achieved primarily through a positive control exerted by the pituitary hormone thyroid stimulating hormone (TSH) and a negative control exerted by iodine. In most physiological circumstances the maintenance of eumetabolism requires steady concentrations of circulating thyroid hormones. This is achieved by a classical chemostat that involves the feedback of thyroid hormones on TSH production. Compared with other endocrine organs, the control of thyroid function is subject to relatively slow changes. The main roles of the regulatory mechanisms are to ensure adequate use of the available iodine in the diet to maintain steady levels of circulating hormones and to protect the thyroid gland and the organism from the toxicity that can result from excessive availability of iodine. Regulation of thyroid function is thus mainly of a “tonic” nature, with virtually no physiological circumstances in which the gland should be put completely at rest. This chapter concentrates on the regulatory actions of thyrotropin via its receptor.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. Dumont JE, Vassart G, Refetoff S. Thyroid disorders. In: Scriver CR, ed. The Metabolic Basis of Inherited Diseases. McGraw-Hill, 1989, pp. 1843–1879.

    Google Scholar 

  2. Vassart G, Dumont JE. The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr Rev 1992;13:596–611.

    PubMed  CAS  Google Scholar 

  3. Maenhaut C, Brabant G, Vassart G, Dumont JE. In vitro and in vivo regulation of thyrotropin receptor mRNA levels in dog and human thyroid cells. J Biol Chem 1992;15:3000–3007.

    Google Scholar 

  4. Damante G, Di Lauro, R. Thyroid-specific gene expression. Biochim Biophys Acta 1994;1218:255–266.

    Article  PubMed  CAS  Google Scholar 

  5. Dumont JE, Lamy F, Roger P, Maenhaut C. Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors. Physiol. Rev 1992;72:667–697.

    PubMed  CAS  Google Scholar 

  6. Vassart G, Parma J, Van Sande J, Dumont J. The thyrotropin receptor and the regulation of thyrocyte function and growth: update 1994. Endocr Rev 1994;3:77–80.

    CAS  Google Scholar 

  7. Roger P, Reuse S, Maenhaut C, Dumont JE. Multiple facets of the modulation of growth by cAMP. Vitam Horm 1995;51:59–191.

    Article  PubMed  CAS  Google Scholar 

  8. Dumont JE, Jauniaux JC, Roger PP. The cyclic AMP-mediated stimulation of cell proliferation. Trends Biochem Sci 1989;14:67–71.

    Article  PubMed  CAS  Google Scholar 

  9. Ledent, C., Dumont JE, Vassart G, Parmentier M. Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism. EMBO J 1992;11:537–542.

    PubMed  CAS  Google Scholar 

  10. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 1991;325:1688–1695.

    Article  PubMed  CAS  Google Scholar 

  11. Parma J, Duprez L, Van Sande J, Cochaux P, Gervy C, Mockel J, Dumont JE, Vassart G. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 1993;365:649–651.

    Article  PubMed  CAS  Google Scholar 

  12. van Sande J, Parma J, Tonacchera M, Swillens S, Dumont J, Vassart G. Somatic and germline mutations of the TSH receptor gene in thyroid diseases. J Clin Endocrinol Metab 1995;80:2577–2585.

    Article  PubMed  Google Scholar 

  13. Duprez L, Parma J, Van Sande J, Allegeier A, Leclére J, Schvartz C, Delisle M, Decoulx M, Orgiazzi J, Dumont J, Vassart G. Germline mutations in the thyrotropin receptor gene cause nonautoimmune autosomal dominant hyperthyroidism. Nat Genet 1994;7:396–401.

    Article  PubMed  CAS  Google Scholar 

  14. Strader CD, Fong TM, Tota MR, Underwood D. Structure and function of G protein-coupled receptors. Annu Rev Biochem 1994;63:101–132.

    Article  PubMed  CAS  Google Scholar 

  15. Nagayama Y, Rapoport B. The thyrotropin receptor 25 years after its discovery: new insight after its molecular cloning. Mol Endocrinol 1992;6:145–156.

    Article  PubMed  CAS  Google Scholar 

  16. Gross B, Misrahi M, Sar S, Milgrom E. Composite structure of the human thyrotropin receptor gene. Biochem Biophys Res Commun 1991;177:679–687.

    Article  PubMed  CAS  Google Scholar 

  17. Kobe B, Deisenhofer J. A structural basis of the interactions between leucine-rich repeats and protein ligands. Nature 1995;374:183–186.

    Article  PubMed  CAS  Google Scholar 

  18. Kobe B, Deisenhofer J. The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci 1994;19:415–421.

    Article  PubMed  CAS  Google Scholar 

  19. Nagayama Y, Russo D, Wadsworth HL, Chazenbalk GD, and Rapoport B. 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. J Biol Chem 1991;266:14926–14930.

    PubMed  CAS  Google Scholar 

  20. Nagayama Y, Wadsworth HL, Chazenbalk GD, Russo D, Seto P, Rapoport B. Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function. Proc Natl Acad Sci USA 1991;88:902–905.

    Article  PubMed  CAS  Google Scholar 

  21. Braun T, Schofield PR, Sprengel R. Amino-terminal leucine-rich repeats in gonadotropin receptors determine hormone selectivity. EMBO J 1991;10:1885–1890.

    PubMed  CAS  Google Scholar 

  22. Segaloff DL, and Ascoli M. The lutropin/choriogonadotropin receptor … 4 years later. Endocr Rev 1993;14:324–347.

    PubMed  CAS  Google Scholar 

  23. Lefkowitz RJ, Cotecchia S, Kjelsberg MA, Pitcher J, Koch WJ, Inglese J, and Caron MG. Adrenergic receptors: recent insights into their mechanism of activation and desensitization. Adv Second Messenger Phosphoprotein Res 1993;28:1–9.

    PubMed  CAS  Google Scholar 

  24. Gether U, Johansen TE, and Schwartz TW. Chimeric NK1 (substance P)/NK3 (neurokinin B) receptors: identification of domains determining the binding specificity of tachykinin agonists. J Biol Chem 1993;268:7893–7898.

    PubMed  CAS  Google Scholar 

  25. Yokota Y, Akazawa C, Ohkubo H, and Nakanishi S. Delineation of structural domains involved in the subtype specificity of tachykinin receptors through chimeric formation of substance P/substance K receptors. EMBO J 1992;11:3585–3591.

    PubMed  CAS  Google Scholar 

  26. Nothacker HP, Grimmelikhuijzen CJ. Molecular cloning of a novel, putative G protein-coupled receptor from sea anemones structurally related to members of the FSH, TSH, LH/CG receptor family from mammals. Biochem Biophys Res Commun 1993;197:1062–1069.

    Article  PubMed  CAS  Google Scholar 

  27. Hauser F, Nothacker H, Grimmelikhuizen C. Molecular cloning, genomic organization and developmental regulation of a novel receptor from Drosophila melanogaster structurally related to members of the TSH, FSH, LH/CG receptor family from mammals. J Biol Chem, 1996; in press.

    Google Scholar 

  28. Hoflack J, Hibert MF, Trumpp Kallmeyer S, and Bidart JM. Three-dimensional models of gonado-thyrotropin hormone receptor transmembrane domain. Drug Des Discov 1993;10:157–171.

    PubMed  CAS  Google Scholar 

  29. Kajava AV, Vassart G, and Wodak SJ. Modeling of the three-dimensional structure of proteins with the typical leucine-rich repeats. Structure 1995;3:867–877.

    Article  PubMed  CAS  Google Scholar 

  30. Laurent E, Mockel J, Van Sande J, Graff I, Dumont JE. Dual activation by thyrotropin of the phospho-lipase C and cyclic AMP cascades in human thyroid. Mol Cell Endocrinol 1987;52:273–278.

    Article  PubMed  CAS  Google Scholar 

  31. Laugwitz KL, Allgeier A, Offermanns S, Spicher K, Van Sande J, Dumont JE, Schultz G. The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. Proc Natl Acad Sci USA 1996;93:116–120.

    Article  PubMed  CAS  Google Scholar 

  32. 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;269:13733–13735.

    PubMed  CAS  Google Scholar 

  33. Miyai K, Azukizawa M, and Kumahara Y. Familial isolated thyrotropin deficiency with cretinism. N Engl JMed 1971;285:1043–1048.

    Article  CAS  Google Scholar 

  34. Hayashizaki Y, Hiraoka Y, Endo Y, Miyai K, and Matsubara K. Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the beta-subunit [published erratum, EMBO J 1989;8:3542]. EMBO J 1989;8:2291–2296.

    PubMed  CAS  Google Scholar 

  35. Hayashizaki Y, Hiraoka Y, Tatsumi K, Hashimoto T, Furuyama J, Miyai K, Nishijo K, Matsuura M, Kohno H, Labbe A, et al.. Deoxyribonucleic acid analyses of five families with familial inherited thyroid stimulating hormone deficiency [see comments]. J Clin Endocrinol Metab 1990;71:792–796.

    Article  PubMed  CAS  Google Scholar 

  36. Stein SA, Shanklin DR, Krulich L, Roth MG, Chubb M, and Adams PM. Evaluation and characterization of the hyt/hyt hypothyroid mouse: II. Abnormalities of TSH and the thyroid gland. Neuro-endocrinology 1989;49:509–519.

    CAS  Google Scholar 

  37. Stein S, Oates E, Hall C, Grumbles R, Fernandez L, Taylor N, Puett D, and Jin S. Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse. Mol Endocrinol 1994;8:129–138.

    Article  PubMed  CAS  Google Scholar 

  38. Stanbury JB, Rocmans P, Buhler UK, and Ochi Y. Congenital hypothyroidism with impaired thyroid response to thyrotropin. N Engl J Med 1968;279:1132–1136.

    Article  PubMed  CAS  Google Scholar 

  39. Codaccioni JL, Carayon P, Michel Bechet M, Foucault F, Lefort G, and Pierron H. Congenital hypothyroidism associated with thyrotropin unresponsiveness and thyroid cell membrane alterations. J Clin Endocrinol Metab 1980;50:932–937.

    Article  PubMed  CAS  Google Scholar 

  40. Takeshita A, Nagayama Y, Yamashita S, Takamatsu J, Oshawa N, Maesaka H, Tachibana K, Tokuhiro E, Ashizawa K, Yokoyama N, and Nagataki S. Sequence analysis of the TSH receptor gene in congenital primary hypothyroidism associated with TSH unresponsiveness. Thyroid 1994;4:255–259.

    Article  PubMed  CAS  Google Scholar 

  41. Sunthornthepvarakul T, Gottschalk M, Hayashi Y, and Refetoff S. Resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. N Engl J Med 1995;332:155–160.

    Article  CAS  Google Scholar 

  42. Biebermann H, Krude H, Thiede C, Kotulla D, Gruters A. Sporadic congenital hypothyroidism due to compound heterozygosity for two mutations of the coding sequence of the TSH receptor gene. Int Congress of Endocrinol. San Francisco, 1996, Abs 1996;1:P2–954

    Google Scholar 

  43. Maenhaut C, Van Sande J, Libert F, Abramowicz M, Parmentier M, Vanderhaegen JJ, Dumont JE, Vassart G, Schiffmann S. RDC8 codes for an adenosine A2 receptor with physiological constitutive activity. Biochem Biophys Res Commun 1990;173:1169–1178.

    Article  PubMed  CAS  Google Scholar 

  44. Michiels FM, Caillou B, Talbot M, Dessarps Freichey F, Maunoury MT, Schlumberger M, Mercken L, Monier R, Feunteun J. Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice. Proc Natl Acad Sci USA 1994;91:10488–10492.

    Article  PubMed  CAS  Google Scholar 

  45. Lyons J, Landis CA, Harsh G, Vallar L, Grunewald K, Feichtinger H, Duh QY, Clark OH, Kawasaki E, Bourne HR, et al. Two G protein oncogenes in human endocrine tumors. Science 1990;249:655–659.

    Article  PubMed  CAS  Google Scholar 

  46. Goretzki PE, Lyons J, Stacy Phipps S, Rosenau W, Demeure M, Clark OH, McCormick F, Roher HD, Bourne HR. Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications. World J Surg 1992;16:576–581.

    Article  PubMed  CAS  Google Scholar 

  47. Suarez HG, du Villard JA, Caillou B, Schlumberger M, Parmentier C, Monier R. gsp mutations in human thyroid tumours. Oncogene 1991;6:677–679.

    PubMed  CAS  Google Scholar 

  48. O’Sullivan C, Barton CM, Staddon SL, Brown CL, Lemoine NR. Activating point mutations of the gsp oncogene in human thyroid adenomas. Mol Carcinog 1991;4:345–349.

    Article  CAS  Google Scholar 

  49. Kjelsberg MA, Cotecchia S, Ostrowski J, Caron MG, Lefkowitz RJ. Constitutive activation of the alpha lB-adrenergic receptor by all amino acid substitutions at a single site: evidence for a region which constrains receptor activation. J Biol Chem 1992;267:1430–1433.

    PubMed  CAS  Google Scholar 

  50. Samama P, Cotecchia S, Costa T, Lefkowitz RJ. A mutation-induced activated state of the beta 2-adrenergic receptor: extending the ternary complex model. J Biol Chem 1993;268:4625–4636.

    PubMed  CAS  Google Scholar 

  51. Cotecchia S, Exum S, Caron MG, Lefkowitz RJ. Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function. Proc Natl Acad Sci USA 1990;87:2896–2900.

    Article  PubMed  CAS  Google Scholar 

  52. Porcellini A, Ciullo I, Laviola L, Amabile A, Fenzi G, Avvedimento V. Novel mutations of thyrotropin receptor gene in thyroid hyperfunctioning adenomas. J Clin Endocrinol Metab 1994;79:657–661.

    Article  PubMed  CAS  Google Scholar 

  53. Paschke R, Tonacchera M, Van Sande J, Parma J, Vassart G. 1994. Identification and functional characterization of two new somatic mutations causing constitutive activation of the TSH receptor in hyperfunctioning autonomous adenomas of the thyroid. J Clin Endocrinol Metab, 1994;79:1785–1789.

    CAS  Google Scholar 

  54. Parma J, Van Sande J, Swillens S, Tonacchera M, Dumont JE, Vassart G. Somatic mutations causing constitutive activity of the TSH receptor are the major cause of hyperfunctional thyroid adenomas: identification of additional mutations activating both the cAMP and inisitolphosphate-Ca++ cascades. Mol Endocrinol 1995;9:725–733.

    Article  PubMed  CAS  Google Scholar 

  55. DE Roux N, Polak M, Couet J, Leger J, Czernichow P, Milgrom E, Misrahi M. A neomutation of the TSH receptor in a severe neonatal hyperthyroidism. J Clin Endocrinol Metab 1996;81:2023–2026.

    Article  PubMed  Google Scholar 

  56. Parma J, Duprez L, Van Sande J, Hermans J, Rocmans P, Van Vliet G, Costagliola S, Rodien P, Dumont JE, Vassart G. Diversity and prevalence of somatic mutations in the TSH receptor and Gs alfa genes as a cause of toxic thyroid adenomas. J Clin Endocrinol Metab 1997;82(8):2695–2701.

    Article  PubMed  CAS  Google Scholar 

  57. Takeshita A, Nagayama Y, Yokoyama N, Ishikawa N, Ito K, Yamashita T, Obara T, Murakami Y, Kuma K, Takamatsu J, et al. Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan. J Clin Endocrinol Metab 1995;80:2607–2611.

    Article  PubMed  CAS  Google Scholar 

  58. Russo D, Arturi F, Wicker R, Chazenbalk GD, Schlumberger M, Du Villard JA, Caillou B, Monier R, Rapoport B, Filetti S, et al. Genetic alterations in thyroid hyperfunctioning adenomas. J Clin Endocrinol Metab 1995;80:1347–1351.

    Article  PubMed  CAS  Google Scholar 

  59. Delange F. Correction of iodine deficiency: benefits and possible side effects. Eur J Endocrinol 1995;132:542–543 (comment).

    Article  PubMed  CAS  Google Scholar 

  60. Russo D, Arturi F, Schlumberger M, Caillou B, Filetti S, Suarez HG. Activating mutations of the TSH receptor in differentiated thyroid carcinomas. Oncogene 1995;11:1907–1911.

    PubMed  CAS  Google Scholar 

  61. Thomas JS, Leclére J, Hartemann P, Duheille J, Orgiazzi J, Petersen M, Janot C, Guedenet JC. Familial hyperthyroidism without evidence of autoimmunity. Acta Endocrinol (Copenh) 1982;100:512–518.

    CAS  Google Scholar 

  62. Tonacchera M, Van Sande J, Cetani F, Swillens S, Schvartz C, Winiszewski L, Portmann L, Dumont JE, Vassart G, Parma J. Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia. J Clin Endocrinol Metab 1996;81:547–554.

    Article  PubMed  CAS  Google Scholar 

  63. Leclere J, Béné M, Duprez A, Faure G, Thomas J, Vignau M, Burlet C. Behavior of thyroid tissue from patients with Graves’ disease in nude mice. J Clin Endocrinol Metab 1984;59:175–177.

    Article  PubMed  CAS  Google Scholar 

  64. Kopp P, Van Sande J, Parma J, Duprez L, Zuppinger K, Jameson JL, Vassart G. Congenital non-autoimmune hyperthyroidism caused by a neomutation in the thyrotropin receptor gene. N Engl J Med 1995;332:150–154.

    Article  PubMed  CAS  Google Scholar 

  65. Kohler B, Biebermann H, Krohn HP, Dralle D, Finke R, Gruters A. A novel germline mutation in the TSH receptor gene causing nonautoimmune congenital hyperthyroidism. Int Congress Endocrinol, San Francisco, 1996, Abst 1996;1:P-946.

    Google Scholar 

  66. Kosugi S, Okajima F, Ban T, Hidaka A, Shenker A, Kohn L. Mutation of Alanine 623 in the third cyto-plasmic loop of the rat TSH receptor results in a loss in the phosphoinositide but not cAMP signal induced by TSH and receptor autoantibodies. J Biol Chem 1992;267:24153–24156.

    PubMed  CAS  Google Scholar 

  67. Eggerickx D, Denef JF, Labbe O, Hayashi Y, Refetoff S, Vassart G, Parmentier M, Libert F. Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase. Biochem J 1995;309:837–843.

    PubMed  CAS  Google Scholar 

  68. Westphal RS, Backstrom JR, Sanders Bush E. Increased basal phosphorylation of the constitutively active serotonin 2C receptor accompanies agonist-mediated desensitization. Mol Pharmacol 1995;48:200–205.

    PubMed  CAS  Google Scholar 

  69. Tiberi M, Caron MG. High agonist-independent activity is a distinguishing feature of the dopamine DlB receptor subtype. J Biol Chem 1994;269:27925–27931.

    PubMed  CAS  Google Scholar 

  70. Chazenbalk GD, Rapoport B. Expression of the extracellular domain of the thyrotropin receptor in the baculovirus system using a promoter active earlier than the polyhedrin promoter: implications for the expression of functional highly glycosylated proteins. J Biol Chem 1995;270:1543–1549.

    Article  PubMed  CAS  Google Scholar 

  71. Ren Q, Kurose H, Lefkowitz RJ, Cotecchia S. Constitutively active mutants of the α2-adrenergic receptor. J Biol Chem 1993;268:16483–16487.

    PubMed  CAS  Google Scholar 

  72. Lefkowitz RJ, Cotecchia S, Samama P, and Costa T. Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins. Trends Pharmacol Sci 1994;14:303–307.

    Article  Google Scholar 

  73. van Sande J, Massart C, Costagliola S, Alleier A, Cetani F, Vassart G, and Dumont JE. Specific activation of the thyrotropin receptor by trypsin. Mol Cell Endocrinol 1996;119:161–168.

    Article  PubMed  Google Scholar 

  74. Zhang ML, Sugawa H, Kosugi S, and Mori T. Constitutive activation of the thyrotropin receptor by deletion of a portion of the extracellular domain. Biochem Biophys Res Commun 1995;211:205–210.

    Article  PubMed  CAS  Google Scholar 

  75. Paschke R, Parmentier M, and Vassart G. Importance of the extracellular domain of the human thyrotrophin receptor for activation of cyclic AMP production. J Mol Endocrinol 1994;13:199–207.

    Article  PubMed  CAS  Google Scholar 

  76. Ji I, Ji T. Human choriogonadotrophin binds to a lutropin receptor with essentially no N-terminal extension and stimulates cAMP synthesis. J Biol Chem 1991;266:1306–1309.

    Google Scholar 

  77. Zeng H, Ji I, and Ji TH. Lys91 and His90 of the alpha-subunit are crucial for receptor binding and hormone action of follicle-stimulating hormone (FSH) and play hormone-specific roles in FSH and human chorionic gonadotropin. Endocrinology 1995;136:2948–2953.

    Article  PubMed  CAS  Google Scholar 

  78. Ji I, Zeng H, and Ji TH. Receptor activation of and signal generation by the lutropin/chorio-gonadotropin receptor: cooperation of Asp397 of the receptor and alpha Lys91 of the hormone. J Biol Chem 1993;268:22971–22974.

    PubMed  CAS  Google Scholar 

  79. Yoo J, Zeng H, Ji I, Murdoch WJ, and Ji TH. COOH-terminal amino acids of the alpha subunit play common and different roles in human choriogonadotropin and follitropin. J Biol Chem 1993;268:13034–13042.

    PubMed  CAS  Google Scholar 

  80. Ji I, and JI T. Receptor activation is distinct from hormone binding in intact lutropion-choriogonadotropin receptors and Asp397 is important for receptor activation. J Biol Chem 1995;268:20851–20854.

    Google Scholar 

  81. Amr S, Shimohigashi Y, Carayon P, Chen HC, and Nisula B. Role of the carbohydrate moiety of human choriogonadotropin in its thyrotropic activity. Arch Biochem Biophys 1984;229:170–176.

    Article  PubMed  CAS  Google Scholar 

  82. Thotakura NR, Weintraub BD, and Bahl OP. The role of carbohydrate in human choriogonadotropin (hCG) action: effects of N-linked carbohydrate chains from hCG and other glycoproteins on hormonal activity. Mol Cell Endocrinol 1990;70:263–272.

    Article  PubMed  CAS  Google Scholar 

  83. Thotakura NR, LiCalzi L, and Weintraub BD. The role of carbohydrate in thyrotropin action assessed by a novel approach using enzymatic deglycosylation. J Biol Chem 1990;265:11527–11534.

    PubMed  CAS  Google Scholar 

  84. Dallas JS, Cunningham SJ, Patibandla SA, Seetharamaiah GS, Morris JC, Tahara K, Kohn LD, and Prabhakar BS. TSH receptor antibodies can inhibit TSH-mediated cAMP production in thyroid cells by either blocking TSH binding or affecting a step subsequent to TSH binding. Endocrinology 1996;137:3329–3339.

    Article  PubMed  CAS  Google Scholar 

  85. Perez DM, DeYoung MB, Graham RM. Coupling of expressed alpha lB-and alpha lD-adrenergic receptor to multiple signaling pathways is both G protein and cell type specific. Mol Pharmacol 1993;44:784–795.

    PubMed  CAS  Google Scholar 

  86. Scheer A, Fanelli F, Costa T, De Benedetti PG, and Cotecchia S. Constitutively active mutants of the alphalb-adrenergic receptor: role of highly conserved polar amino acids in receptor activation. EMBO J 1996;15:3566–3578.

    PubMed  CAS  Google Scholar 

  87. Abramowicz M, Duprez L, Parma J, Vassart G, and Heinrichs C. Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest 1997;99(12):3018–3024.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Gilbert Vassart MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Allen M. Spiegel MD (Chief, Metabolic Diseases Branch) (Chief, Metabolic Diseases Branch)

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Vassart, G. (1998). Hypo- and Hyperthyroidism Caused by Mutations of the TSH Receptor. In: Spiegel, A.M. (eds) G Proteins, Receptors, and Disease. Contemporary Endocrinology, vol 6. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-1802-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-1802-9_7

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-7290-8

  • Online ISBN: 978-1-4612-1802-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation