The Thyrotropin Receptor in Thyroid Diseases

doi:10.1056/NEJM199712043372307

Volume 337:1675-1681		December 4, 1997		Number 23

The Thyrotropin Receptor in Thyroid Diseases

Ralf Paschke, M.D., and Marian Ludgate, Ph.D.

Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

Full Text

PDF

Purchase this article

Add to Personal Archive

Add to Citation Manager

Notify a Friend

E-mail When Cited

PubMed Citation

The growth and function of the thyroid are controlled by thyrotropin¹through the activation of its receptor, which belongs to thelarge family of G protein–coupled receptors. Despite theextreme diversity of their ligands, all receptors from thisfamily have a common molecular architecture: seven transmembranesegments, three extracellular loops, three intracellular loops,an extracellular amino terminal, and an intracytoplasmic carboxyterminal (Figure 1). The glycoprotein hormone receptors constitutea subfamily that is characterized mainly by a particularly longamino-terminal extracellular domain that confers binding specificity.¹^,²¹

View larger version (42K):
[in this window]
[in a new window]
Figure 1. The Thyrotropin Receptor.
The location of constitutively activating mutations¹^,²^,³^,⁴^,⁵^,⁶^,⁷^,⁸^,⁹^,¹⁰^,¹¹^,¹²^,¹³^,¹⁴^,¹⁵^,¹⁶ and inactivating mutations¹⁵^,¹⁷^,¹⁸ . . . [Full Text of this Article]

Autonomously Functioning Thyroid Adenomas

Differentiated Thyroid Cancer

Germ-Line Mutations in the Thyrotropin Receptor in Autosomal Dominant Nonautoimmune Hyperthyroidism

Thyrotropin Resistance

The Thyrotropin Receptor and Autoimmunity

Conclusions

Source Information

From the Department of Internal Medicine III, University of Leipzig, Leipzig, Germany (R.P.), and the Department of Pathology, University of Wales College of Medicine, Cardiff, United Kingdom (M.L.). This article is dedicated to the memory of Olaf Heine, M.D.

Address reprint requests to Dr. Paschke at Department of Internal Medicine III, University of Leipzig, Ph. Rosenthal Str. 27, 04103 Leipzig, Germany.

References

This article has been cited by other articles:

Zhang, L., Bowen, T., Grennan-Jones, F., Paddon, C., Giles, P., Webber, J., Steadman, R., Ludgate, M. (2009). Thyrotropin Receptor Activation Increases Hyaluronan Production in Preadipocyte Fibroblasts: CONTRIBUTORY ROLE IN HYALURONAN ACCUMULATION IN THYROID DYSFUNCTION. J. Biol. Chem. 284: 26447-26455 [Abstract] [Full Text]
Zhang, L., Paddon, C., Lewis, M. D, Grennan-Jones, F., Ludgate, M. (2009). Gs{alpha} signalling suppresses PPAR{gamma}2 generation and inhibits 3T3L1 adipogenesis. J Endocrinol 202: 207-215 [Abstract] [Full Text]
Rivas, M., Mellstrom, B., Torres, B., Cali, G., Ferrara, A. M., Terracciano, D., Zannini, M., Morreale de Escobar, G., Naranjo, J. R. (2009). The DREAM Protein Is Associated with Thyroid Enlargement and Nodular Development. Mol. Endocrinol. 23: 862-870 [Abstract] [Full Text]
Heemstra, K. A, Toes, R. E, Sepers, J., Pereira, A. M, Corssmit, E. P, Huizinga, T. W J, Romijn, J. A, Smit, J. W (2008). Rituximab in relapsing Graves' disease, a phase II study. Eur J Endocrinol 159: 609-615 [Abstract] [Full Text]
Chen, M.-H., Liao, S.-L., Chen, M.-H., Tsou, P.-L., Shih, M.-J., Chang, T.-C., Chuang, L.-M. (2008). Lysosome-Related Genes Are Regulated in the Orbital Fat of Patients with Graves' Ophthalmopathy. IOVS 49: 4760-4764 [Abstract] [Full Text]
Zhang, L., Baker, G., Janus, D., Paddon, C. A., Fuhrer, D., Ludgate, M. (2006). Biological Effects of Thyrotropin Receptor Activation on Human Orbital Preadipocytes. IOVS 47: 5197-5203 [Abstract] [Full Text]
Jaschke, H., Neumann, S., Moore, S., Thomas, C. J., Colson, A.-O., Costanzi, S., Kleinau, G., Jiang, J.-K., Paschke, R., Raaka, B. M., Krause, G., Gershengorn, M. C. (2006). A Low Molecular Weight Agonist Signals by Binding to the Transmembrane Domain of Thyroid-stimulating Hormone Receptor (TSHR) and Luteinizing Hormone/Chorionic Gonadotropin Receptor (LHCGR). J. Biol. Chem. 281: 9841-9844 [Abstract] [Full Text]
Jaeschke, H., Neumann, S., Kleinau, G., Mueller, S., Claus, M., Krause, G., Paschke, R. (2006). An Aromatic Environment in the Vicinity of Serine 281 Is a Structural Requirement for Thyrotropin Receptor Function. Endocrinology 147: 1753-1760 [Abstract] [Full Text]
Shih, M.-J., Liao, S.-L., Kuo, K.-T., Smith, T. J., Chuang, L.-M. (2006). Molecular Pathology of Muller's Muscle in Graves' Ophthalmopathy. J. Clin. Endocrinol. Metab. 91: 1159-1167 [Abstract] [Full Text]
Wettschureck, N., Offermanns, S. (2005). Mammalian G Proteins and Their Cell Type Specific Functions. Physiol. Rev. 85: 1159-1204 [Abstract] [Full Text]
Krohn, K., Fuhrer, D., Bayer, Y., Eszlinger, M., Brauer, V., Neumann, S., Paschke, R. (2005). Molecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter. Endocr. Rev. 26: 504-524 [Abstract] [Full Text]
Neumann, S., Claus, M., Paschke, R. (2005). Interactions between the extracellular domain and the extracellular loops as well as the 6th transmembrane domain are necessary for TSH receptor activation. Eur J Endocrinol 152: 625-634 [Abstract] [Full Text]
Al-Khafaji, F, Wiltshire, M, Fuhrer, D, Mazziotti, G, Lewis, M D, Smith, P J, Ludgate, M (2005). Biological activity of activating thyrotrophin receptor mutants: modulation by iodide. J Mol Endocrinol 34: 209-220 [Abstract] [Full Text]
Baker, G., Mazziotti, G., von Ruhland, C., Ludgate, M. (2005). Reevaluating Thyrotropin Receptor-Induced Mouse Models of Graves' Disease and Ophthalmopathy. Endocrinology 146: 835-844 [Abstract] [Full Text]
Neumann, S., Krause, G., Claus, M., Paschke, R. (2005). Structural Determinants for G Protein Activation and Selectivity in the Second Intracellular Loop of the Thyrotropin Receptor. Endocrinology 146: 477-485 [Abstract] [Full Text]
Guo, T-W, Zhang, F-C, Yang, M-S, Gao, X-C, Bian, L, Duan, S-W, Zheng, Z-J, Gao, J-J, Wang, H, Li, R-L, Feng, G-Y, St Clair, D, He, L (2004). Positive association of the DIO2 (deiodinase type 2) gene with mental retardation in the iodine-deficient areas of China. J. Med. Genet. 41: 585-590 [Abstract] [Full Text]
Mizrachi, D., Segaloff, D. L. (2004). Intracellularly Located Misfolded Glycoprotein Hormone Receptors Associate with Different Chaperone Proteins than Their Cognate Wild-Type Receptors. Mol. Endocrinol. 18: 1768-1777 [Abstract] [Full Text]
Fuhrer, D., Lewis, M. D., Alkhafaji, F., Starkey, K., Paschke, R., Wynford-Thomas, D., Eggo, M., Ludgate, M. (2003). Biological Activity of Activating Thyroid-Stimulating Hormone Receptor Mutants Depends on the Cellular Context. Endocrinology 144: 4018-4030 [Abstract] [Full Text]
Peeters, R. P., van Toor, H., Klootwijk, W., de Rijke, Y. B., Kuiper, G. G. J. M., Uitterlinden, A. G., Visser, T. J. (2003). Polymorphisms in Thyroid Hormone Pathway Genes Are Associated with Plasma TSH and Iodothyronine Levels in Healthy Subjects. J. Clin. Endocrinol. Metab. 88: 2880-2888 [Abstract] [Full Text]
Iacovelli, L., Capobianco, L., Salvatore, L., Sallese, M., D'Ancona, G. M., De Blasi, A. (2001). Thyrotropin Activates Mitogen-Activated Protein Kinase Pathway in FRTL-5 by a cAMP-Dependent Protein Kinase A-Independent Mechanism. Mol. Pharmacol. 60: 924-933 [Abstract] [Full Text]
Eszlinger, M., Krohn, K., Paschke, R. (2001). Complementary DNA Expression Array Analysis Suggests a Lower Expression of Signal Transduction Proteins and Receptors in Cold and Hot Thyroid Nodules. J. Clin. Endocrinol. Metab. 86: 4834-4842 [Abstract] [Full Text]
Neumann, S., Krause, G., Chey, S., Paschke, R. (2001). A Free Carboxylate Oxygen in the Side Chain of Position 674 in Transmembrane Domain 7 Is Necessary for TSH Receptor Activation. Mol. Endocrinol. 15: 1294-1305 [Abstract] [Full Text]
Winter, W. E., Signorino, M. R. (2001). Molecular Thyroidology. Annals of Clinical & Laboratory Science 31: 221-244 [Abstract] [Full Text]
Krohn, K., Paschke, R. (2001). Progress in Understanding the Etiology of Thyroid Autonomy. J. Clin. Endocrinol. Metab. 86: 3336-3345 [Full Text]
Yen, P. M. (2001). Physiological and Molecular Basis of Thyroid Hormone Action. Physiol. Rev. 81: 1097-1142 [Abstract] [Full Text]
Wilson, J. D. (2001). Prospects for Research for Disorders of the Endocrine System. JAMA 285: 624-627 [Abstract] [Full Text]
Latronico, A. C., Shinozaki, H., Guerra, G. Jr., Pereira, M. A. A., Lemos Marini, S. H. V., Baptista, M. T. M., Arnhold, I. J. P., Fanelli, F., Mendonca, B. B., Segaloff, D. L. (2000). Gonadotropin-Independent Precocious Puberty Due to Luteinizing Hormone Receptor Mutations in Brazilian Boys: A Novel Constitutively Activating Mutation in the First Transmembrane Helix. J. Clin. Endocrinol. Metab. 85: 4799-4805 [Abstract] [Full Text]
Grunwald, F., Biersack, H.-J. (2000). FDG PET in Thyroid Cancer: Thyroxine or Not?. JNM 41: 1996-1998 [Full Text]
Russo, D., Betterle, C., Arturi, F., Chiefari, E., Girelli, M. E., Filetti, S. (2000). A Novel Mutation in the Thyrotropin (TSH) Receptor Gene Causing Loss of TSH Binding But Constitutive Receptor Activation in a Family with Resistance to TSH. J. Clin. Endocrinol. Metab. 85: 4238-4242 [Abstract] [Full Text]
Weetman, A. P. (2000). Graves' Disease. NEJM 343: 1236-1248 [Full Text]
Crisp, M., Starkey, K. J., Lane, C., Ham, J., Ludgate, M. (2000). Adipogenesis in Thyroid Eye Disease. IOVS 41: 3249-3255 [Abstract] [Full Text]
Carroll, R. E., Ostrovskiy, D., Lee, S., Danilkovich, A., Benya, R. V. (2000). Characterization of Gastrin-Releasing Peptide and Its Receptor Aberrantly Expressed by Human Colon Cancer Cell Lines. Mol. Pharmacol. 58: 601-607 [Abstract] [Full Text]
Lazarus, J H, Obuobie, K (2000). Thyroid disorders---an update. Postgrad. Med. J. 76: 529-536 [Full Text]
Tao, Y.-X., Abell, A. N., Liu, X., Nakamura, K., Segaloff, D. L. (2000). Constitutive Activation of G Protein-Coupled Receptors as a Result of Selective Substitution of a Conserved Leucine Residue in Transmembrane Helix III. Mol. Endocrinol. 14: 1272-1282 [Abstract] [Full Text]
Liu, G., Duranteau, L., Carel, J.-C., Monroe, J., Doyle, D. A., Shenker, A. (1999). Leydig-Cell Tumors Caused by an Activating Mutation of the Gene Encoding the Luteinizing Hormone Receptor. NEJM 341: 1731-1736 [Full Text]
Baranski, T. J., Herzmark, P., Lichtarge, O., Gerber, B. O., Trueheart, J., Meng, E. C., Iiri, T., Sheikh, S. P., Bourne, H. R. (1999). C5a Receptor Activation. GENETIC IDENTIFICATION OF CRITICAL RESIDUES IN FOUR TRANSMEMBRANE HELICES. J. Biol. Chem. 274: 15757-15765 [Abstract] [Full Text]
Kovoor, A., Celver, J., Abdryashitov, R. I., Chavkin, C., Gurevich, V. V. (1999). Targeted Construction of Phosphorylation-independent beta -Arrestin Mutants with Constitutive Activity in Cells. J. Biol. Chem. 274: 6831-6834 [Abstract] [Full Text]
Derwahl, M., Broecker, M., Kraiem, Z. (1999). Thyrotropin May Not Be the Dominant Growth Factor in Benign and Malignant Thyroid Tumors. J. Clin. Endocrinol. Metab. 84: 829-834 [Full Text]
Schulz, A., Schöneberg, T., Paschke, R., Schultz, G., Gudermann, T. (1999). Role of the Third Intracellular Loop for the Activation of Gonadotropin Receptors. Mol. Endocrinol. 13: 181-190 [Abstract] [Full Text]
Schaffer, K., McBride, E. W., Beinborn, M., Kopin, A. S. (1998). Interspecies Polymorphisms Confer Constitutive Activity to the Mastomys Cholecystokinin-B/Gastrin Receptor. J. Biol. Chem. 273: 28779-28784 [Abstract] [Full Text]
Latronico, A. C., Abell, A. N., Arnhold, I. J. P., Liu, X., Lins, T. S. S., Brito, V. N., Billerbeck, A. E., Segaloff, D. L., Mendonca, B. B. (1998). A Unique Constitutively Activating Mutation in Third Transmembrane Helix of Luteinizing Hormone Receptor Causes Sporadic Male Gonadotropin-Independent Precocious Puberty. J. Clin. Endocrinol. Metab. 83: 2435-2440 [Abstract] [Full Text]
Litzenburger, T., Fassler, R., Bauer, J., Lassmann, H., Linington, C., Wekerle, H., Iglesias, A. (1998). B Lymphocytes Producing Demyelinating Autoantibodies: Development and Function in Gene-targeted Transgenic Mice. JEM 188: 169-180 [Abstract] [Full Text]
Wonerow, P., Schoneberg, T., Schultz, G., Gudermann, T., Paschke, R. (1998). Deletions in the Third Intracellular Loop of the Thyrotropin Receptor. A NEW MECHANISM FOR CONSTITUTIVE ACTIVATION. J. Biol. Chem. 273: 7900-7905 [Abstract] [Full Text]

Comments and questions? Please contact us.