TSHR as a therapeutic target in Graves’ disease

References

• Smith TJ, Hegedus L. Graves’ disease. N Engl J Med. 2016;375:1552–1565.
   PubMed Web of Science ®Google Scholar
• Adams DD, Purves HD. The role of thyrotrophin in hyperthyroidism and exophthalmos. Metabolism. 1957;6:26–35.
   PubMed Web of Science ®Google Scholar
• Kendall-Taylor P. Effects of long-acting thyroid stimulator (LATS) and LATS protector on human thyroid adenyl cyclase activity. Br Med J. 1973;3:2–75.
   PubMedGoogle Scholar
• Bahn RS. Current insights into the pathogenesis of Graves’ ophthalmopathy. Horm Metab Res. 2015;47:773–778.
   PubMed Web of Science ®Google Scholar
• Wang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014;55:1735–1748.
   PubMed Web of Science ®Google Scholar
• Feliciello A, Porcellini A, Ciullo I, et al. Expression of thyrotropin-receptor mRNA in healthy and Graves’ disease retro-orbital tissue. Lancet. 1993;342:337–338.
   PubMed Web of Science ®Google Scholar
• Bahn RS. Thyrotropin receptor expression in orbital adipose/connective tissues from patients with thyroid-associated ophthalmopathy. Thyroid. 2002;12:193–195.
   PubMed Web of Science ®Google Scholar
• Szkudlinski MW, Fremont V, Ronin C, et al. Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Physiol Rev. 2002;82:473–502.
   PubMed Web of Science ®Google Scholar
• Amir SM, Carraway TF Jr, Kohn LD, et al. The binding of thyrotropin to isolated bovine thyroid plasma membranes. J Biol Chem. 1973;248:4092–4100.
   PubMed Web of Science ®Google Scholar
• Parmentier M, Libert F, Maenhaut C, et al. Molecular cloning of the thyrotropin receptor. Science. 1989;246:1620–1622.
   PubMed Web of Science ®Google Scholar
• Kleinau G, Krause G. Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr Rev. 2009;30:133–151.
   PubMed Web of Science ®Google Scholar
• Postiglione MP, Parlato R, Rodriguez-Mallon A, et al. Role of the thyroid-stimulating hormone receptor signaling in development and differentiation of the thyroid gland. Proc Natl Acad Sci USA. 2002;99:15462–15467.
   PubMed Web of Science ®Google Scholar
• Rapoport B, Aliesky HA, Chen CR, et al. Evidence that TSH receptor A-subunit multimers, not monomers, drive antibody affinity maturation in Graves’ disease. J Clin Endocrinol Metab. 2015;100:E871–5.
   Google Scholar
• Cornelis S, Uttenweiler-Joseph S, Panneels V, et al. Purification and characterization of a soluble bioactive amino-terminal extracellular domain of the human thyrotropin receptor. Biochemistry. 2001;40:9860–9869.
   PubMed Web of Science ®Google Scholar
• Sanders P, Young S, Sanders J, et al. Crystal structure of the TSH receptor (TSHR) bound to a blocking-type TSHR autoantibody. J Mol Endocrinol. 2011;46:81–99.
   PubMed Web of Science ®Google Scholar
• Sanders J, Chirgadze DY, Sanders P, et al. Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody. Thyroid. 2007;17:395–410.
   PubMed Web of Science ®Google Scholar
• Rapoport B, McLachlan SM. TSH receptor cleavage into subunits and shedding of the A-subunit; a molecular and clinical perspective. Endocr Rev. 2016;37:114–134.
   PubMed Web of Science ®Google Scholar
• Schaarschmidt J, Nagel MB, Huth S, et al. Rearrangement of the extracellular domain/extracellular loop 1 interface is critical for thyrotropin receptor activation. J Biol Chem. 2016;291:14095–14108.
   PubMed Web of Science ®Google Scholar
• De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016;388:906–918.
   PubMed Web of Science ®Google Scholar
• Kleinau G, Neumann S, Grüters A, et al. Novel insights on thyroid-stimulating hormone receptor signal transduction. Endocr Rev. 2013;34:691–724.
   PubMed Web of Science ®Google Scholar
• Morshed SA, Latif R, Davies TF. Characterization of thyrotropin receptor antibody-induced signaling cascades. Endocrinology. 2009;150:519–529.
   PubMed Web of Science ®Google Scholar
• Diana T, Li Y, Olivo PD, et al. Analytical performance and validation of a bioassay for thyroid-blocking antibodies. Thyroid. 2016;26:734–740.
   PubMed Web of Science ®Google Scholar
• Huth S, Jaeschke H, Schaarschmidt J, et al. Controversial constitutive TSHR activity: patients, physiology, and in vitro characterization. Horm Metab Res. 2014;46:453–461.
   PubMed Web of Science ®Google Scholar
• Parma J, Duprez L, Van Sande J, et al. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature. 1993;365:649–651.
   PubMed Web of Science ®Google Scholar
• Vassart G, Kleinau G. TSH receptor mutations and diseases. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-2014 Mar 30.
   Google Scholar
• Parma J, Duprez L, Van Sande J, et al. Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. J Clin Endocrinol Metab. 1997;82:2695–2701.
   PubMed Web of Science ®Google Scholar
• Kopp P, Muirhead S, Jourdain N, et al. Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281–>isoleucine) in the extracellular domain of the thyrotropin receptor. J Clin Invest. 1997;100:1634–1639.
   PubMed Web of Science ®Google Scholar
• Duprez L, Parma J, Van Sande J, et al. Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat Genet. 1994;7:396–401.
   PubMed Web of Science ®Google Scholar
• Laugwitz KL, Allgeier A, Offermanns S, et al. Schultz G. The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. Proc Nat Acad Sci (USA). 1996;93:116–120.
   PubMed Web of Science ®Google Scholar
• Vassart G, Dumont JE. The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr Rev. 1992;13:596–611.
   PubMed Web of Science ®Google Scholar
• Boutin A, Eliseeva E, Gershengorn MC, et al. β-Arrestin-1 mediates thyrotropin-enhanced osteoblast differentiation. Faseb J. 2014;28:3446–3455.
   PubMed Web of Science ®Google Scholar
• Frenzel R, Voigt C, Paschke R. The human thyrotropin receptor is predominantly internalized by beta-arrestin 2. Endocrinology. 2006;147:3114–3122.
   PubMed Web of Science ®Google Scholar
• Luttrell LM, Lefkowitz RJ. The role of beta arrestins in the termination and transduction of G-protein coupled receptor signals. J Cell Sci. 2002;115:455–465.
   PubMed Web of Science ®Google Scholar
• Povsic TJ, Kohout TA, Lefkowitz RJ. Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis. J Biol Chem. 2003;278:51334–51339.
   PubMed Web of Science ®Google Scholar
• Smith TJ. Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? Pharmacol Rev. 2010;62:199–236.
   PubMed Web of Science ®Google Scholar
• Girnita L, Worrall C, Takahashi S, et al. Something old, something new and something borrowed: emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation. Cell Mol Life Sci. 2014;71:2403–2427.
   PubMed Web of Science ®Google Scholar
• Gallagher EJ, LeRoith D. Minireview: IGF, insulin, and cancer. Endocrinology. 2011;152:2546–2551.
   PubMed Web of Science ®Google Scholar
• Weightman DR, Perros P, Sherif IH, et al. Autoantibodies to IGF-1 binding sites in thyroid associated ophthalmopathy. Autoimmunity. 1993;16:251–257.
   PubMed Web of Science ®Google Scholar
• Pritchard J, Han R, Horst N, et al. Immunoglobulin activation of T cell chemoattractant expression in fibroblasts from patients with Graves’ disease is mediated through the insulin-like growth factor I receptor pathway. J Immunol. 2003;170:6348–6354.
   PubMed Web of Science ®Google Scholar
• Pritchard J, Horst N, Cruikshank W, et al. Igs from patients with Graves’ disease induce the expression of T cell chemoattractants in their fibroblasts. J Immunol. 2002;168:942–950.
   PubMed Web of Science ®Google Scholar
• Tramontano D, Cushing GW, Moses AC, et al. Insulin-like growth factor-I stimulates the growth of rat thyroid cells in culture and synergizes the stimulation of DNA synthesis induced by TSH and Graves’-IgG. Endocrinology. 1986;119:940–942.
   PubMed Web of Science ®Google Scholar
• Ock S, Ahn J, Lee SH, et al. IGF-1 receptor deficiency in thyrocytes impairs thyroid hormone secretion and completely inhibits TSH-stimulated goiter. Faseb J. 2013;27:4899–4908.
   PubMed Web of Science ®Google Scholar
• Clément S, Refetoff S, Robaye B, et al. Low TSH requirement and goiter in transgenic mice overexpressing IGF-I and IGF-I receptor in the thyroid gland. Endocrinology. 2001;142:5131–5139.
   PubMed Web of Science ®Google Scholar
• Tsui S, Naik V, Hoa N, et al. Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves’ disease. J Immunol. 2008;181:4397–4405.
   PubMed Web of Science ®Google Scholar
• Hoa N, Tsui S, Afifiyan NF, et al. Nuclear targeting of IGF-1 receptor in orbital fibroblasts from Graves’ disease: apparent role of ADAM17. Plos One. 2012;7:e34173.
   Google Scholar
• Krieger CC, Place RF, Bevilacqua C, et al. TSH/IGF-1 receptor cross talk in Graves’ ophthalmopathy pathogenesis. J Clin Endocrinol Metab. 2016;101:2340–2347.
   PubMed Web of Science ®Google Scholar
• Weetman AP, Yateman ME, Ealey PA, et al. Thyroid-stimulating antibody activity between different immunoglobulin G subclasses. J Clin Invest. 1990;86:723–727.
   PubMed Web of Science ®Google Scholar
• Neumann S, Place RF, Krieger CC, et al. Future prospects for the treatment of Graves’ hyperthyroidism and eye disease. Horm Metab Res. 2015;47:789–796.
   PubMed Web of Science ®Google Scholar
• Furmaniak J, Sanders J, Nunez Miguel R, et al. Mechanisms of action of TSHR autoantibodies. Horm Metab Res. 2015;47:735–752.
   PubMed Web of Science ®Google Scholar
• Sanders J, Miguel RN, Furmaniak J, et al. TSH receptor monoclonal antibodies with agonist, antagonist, and inverse agonist activities. Methods Enzymol. 2010;485:393–420.
   PubMed Web of Science ®Google Scholar
• Jeffreys J, Depraetere H, Sanders J, et al. Characterization of the thyrotropin binding pocket. Thyroid. 2002;12:1051–1061.
   PubMed Web of Science ®Google Scholar
• Sanders J, Allen F, Jeffreys J, et al. Characteristics of a monoclonal antibody to the thyrotropin receptor that acts as a powerful thyroid-stimulating autoantibody antagonist. Thyroid. 2005;15:672–682.
   PubMed Web of Science ®Google Scholar
• Chen CR, McLachlan SM, Rapoport B. A monoclonal antibody with thyrotropin (TSH) receptor inverse agonist and TSH antagonist activities binds to the receptor hinge region as well as to the leucine-rich domain. Endocrinology. 2009;150:3401–3408.
   PubMed Web of Science ®Google Scholar
• Rees Smith B, Sanders J, Evans M, et al. TSH receptor - autoantibody interactions. Horm Metab Res. 2009;41:448–455.
   PubMed Web of Science ®Google Scholar
• Sanders J, Evans M, Betterle C, et al. A human monoclonal autoantibody to the thyrotropin receptor with thyroid-stimulating blocking activity. Thyroid. 2008;18:735–746.
   PubMed Web of Science ®Google Scholar
• Evans M, Sanders J, Tagami T, et al. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrinol (Oxf). 2010;73:404–412.
   PubMed Web of Science ®Google Scholar
• Furmaniak J, Sanders J, Rees Smith B. Blocking type TSH receptor antibodies. Auto Immun Highlights. 2012;4:11–26.
   PubMedGoogle Scholar
• Jäschke H, Neumann S, Moore S, et al. 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. 2006;281:9841–9844.
   PubMed Web of Science ®Google Scholar
• Neumann S, Kleinau G, Costanzi S, et al. A low-molecular-weight antagonist for the human thyrotropin receptor with therapeutic potential for hyperthyroidism. Endocrinology. 2008;149:5945–5950.
   PubMed Web of Science ®Google Scholar
• Neumann S, Huang W, Eliseeva E, et al. A small molecule inverse agonist for the human thyroid-stimulating hormone receptor. Endocrinology. 2010;151:3454–3459.
   PubMed Web of Science ®Google Scholar
• Turcu AF, Kumar S, Neumann S, et al. A small molecule antagonist inhibits thyrotropin receptor antibody-induced orbital fibroblast functions involved in the pathogenesis of Graves’ ophthalmopathy. J Clin Endocrinol Metab. 2013;98:2153–2159.
   PubMed Web of Science ®Google Scholar
• Neumann S, Pope A, Geras-Raaka E, et al. A drug-like antagonist inhibits thyrotropin receptor–mediated stimulation of cAMP production in Graves’ orbital fibroblasts. Thyroid. 2012;22:839–843.
   PubMed Web of Science ®Google Scholar
• Neumann S, Eliseeva E, McCoy JG, et al. A new small-molecule antagonist inhibits Graves’ disease antibody activation of the TSH receptor. J Clin Endocrinol Metab. 2011;96:548–554.
   PubMed Web of Science ®Google Scholar
• Neumann S, Nir EA, Eliseeva E, et al. A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice. Endocrinology. 2014;155:310–314.
   PubMed Web of Science ®Google Scholar
• Cj VZ, Cj VK, Ov S, et al. Complete inhibition of rhTSH-, Graves’ disease IgG-, and M22-induced cAMP production in differentiated orbital fibroblasts by a low-molecular-weight TSHR antagonist. J Clin Endocrinol Metab. 2012;97:E781–5.
   Google Scholar
• Chen H, Mester T, Raychaudhuri N, et al. Teprotumumab, an IGF-1R blocking monoclonal antibody inhibits TSH and IGF-1 action in fibrocytes. J Clin Endocrinol Metab. 2014;99:E1635–40.
   PubMed Web of Science ®Google Scholar
• Kurzrock R, Patnaik A, Aisner J, et al. A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors. Clin Cancer Res. 2010;16:2458–2465.
   PubMed Web of Science ®Google Scholar
• O’Hayre M, Vázquez-Prado J, Kufareva I, et al. The emerging mutational landscape of g-proteins and g-protein coupled receptors in cancer. Nat Rev Cancer. 2013;13:412–424.
   PubMed Web of Science ®Google Scholar