| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Division of Endocrinology, Mayo Clinic/Foundation (R.S.B., C.M.D., N.N.), Rochester, Minnesota 55905; and Medizinische Klinik, Klinikum Innenstadt, University of Munich (W.J., C.S., A.E.H.), 80336 Munich, Germany
Address all correspondence and requests for reprints to: Rebecca S. Bahn, M.D., Division of Endocrinology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. E-mail: bahn.rebecca{at}mayo.edu
It is acknowledged that the TSH receptor (TSHr) on thyroid follicular cells is the autoantigen involved in the hyperthyroidism of Graves’ disease. However, whether this receptor is expressed in extrathyroidal tissues, and whether it participates directly in the pathogenesis of Graves’ ophthalmopathy (GO) are unclear. We sought to detect the expression of TSHr messenger ribonucleic acid (mRNA) and protein in orbital adipose/connective tissue specimens and in human orbital preadipocyte fibroblast cultures using liquid hybridization analysis and immunohistochemical methods. We demonstrated intact and variant TSHr mRNA transcripts and TSHr-like immunoreactivity in orbital adipose/connective tissue specimens from patients with GO. In addition, TSHr-like immunoreactivity was detected in early passage GO preadipocyte fibroblast cultures that were shown to include some adipose cells. In contrast, neither TSHr mRNA nor protein was detected in normal orbital adipose/connective tissue specimens or in late passage GO orbital fibroblast cultures containing no lipid-laden adipose cells.
In conclusion, we showed that TSHr is expressed in the adipose/connective tissue of the diseased orbit in GO. In addition, TSHr is demonstrable in early passage GO preadipocyte orbital fibroblast cultures that contain a subpopulation of adipocytes. Subsequent passaging of these cells results in the loss of both TSHr expression and adipocyte-specific staining. These results suggest that both the expression of this receptor and the accumulation of adipose tissue in the orbit in GO may be induced in vivo by a humoral factor(s) not present in the cell culture environment.
This article has been cited by other articles:
 |
|
 |
|
  M. Lu and R.-Y. Lin TSH stimulates adipogenesis in mouse embryonic stem cells J. Endocrinol., January 1, 2008; 196(1): 159 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P Peeters, W. M van der Deure, and T. J Visser Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. Eur. J. Endocrinol., November 1, 2006; 155(5): 655 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Gilbert, S. L. Kalled, J. Moorhead, D. M. Hess, P. Rennert, Z. Li, M. Z. Khan, and J. P. Banga Treatment of Autoimmune Hyperthyroidism in a Murine Model of Graves' Disease with Tumor Necrosis Factor-Family Ligand Inhibitors Suggests a Key Role for B Cell Activating Factor in Disease Pathology Endocrinology, October 1, 2006; 147(10): 4561 - 4568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Eckstein, M. Plicht, H. Lax, M. Neuhauser, K. Mann, S. Lederbogen, C. Heckmann, J. Esser, and N. G. Morgenthaler Thyrotropin Receptor Autoantibodies Are Independent Risk Factors for Graves' Ophthalmopathy and Help to Predict Severity and Outcome of the Disease J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3464 - 3470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Schaffler, U. Muller-Ladner, J. Scholmerich, and C. Buchler Role of Adipose Tissue as an Inflammatory Organ in Human Diseases Endocr. Rev., August 1, 2006; 27(5): 449 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kumar, A. Leontovich, M. J. Coenen, and R. S. Bahn Gene Expression Profiling of Orbital Adipose Tissue from Patients with Graves' Ophthalmopathy: A Potential Role for Secreted Frizzled-Related Protein-1 in Orbital Adipogenesis J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4730 - 4735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lantz, T. Vondrichova, H. Parikh, C. Frenander, M. Ridderstrale, P. Asman, M. Aberg, L. Groop, and B. Hallengren Overexpression of Immediate Early Genes in Active Graves' Ophthalmopathy J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4784 - 4791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Boschi, C. Daumerie, M Spiritus, C Beguin, M Senou, D Yuksel, M Duplicy, S Costagliola, M Ludgate, and M C Many Quantification of cells expressing the thyrotropin receptor in extraocular muscles in thyroid associated orbitopathy Br. J. Ophthalmol., June 1, 2005; 89(6): 724 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Agretti, G. De Marco, M. De Servi, C. Marcocci, P. Vitti, A. Pinchera, and M. Tonacchera Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation Eur. J. Endocrinol., May 1, 2005; 152(5): 777 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Smith and N. Hoa Immunoglobulins from Patients with Graves' Disease Induce Hyaluronan Synthesis in Their Orbital Fibroblasts through the Self-Antigen, Insulin-Like Growth Factor-I Receptor J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5076 - 5080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kumar, M. J. Coenen, P. E. Scherer, and R. S. Bahn Evidence for Enhanced Adipogenesis in the Orbits of Patients with Graves' Ophthalmopathy J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 930 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Prabhakar, R. S. Bahn, and T. J. Smith Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy Endocr. Rev., December 1, 2003; 24(6): 802 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pritchard, R. Han, N. Horst, W. W. Cruikshank, and T. J. Smith 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., June 15, 2003; 170(12): 6348 - 6354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Bahn Pathophysiology of Graves' Ophthalmopathy: The Cycle of Disease J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 1939 - 1946. [Full Text] [PDF]
|
|
|
|
 |
|
 G P Fadini, S Nabili, D W McCarey, B Browne, and H A Capell A case of orbital myositis associated with rheumatoid arthritis Ann Rheum Dis, April 1, 2003; 62(4): 383 - 383. [Full Text]
|
|
|
|
|
|
K. Starkey, A. Heufelder, G. Baker, W. Joba, M. Evans, S. Davies, and M. Ludgate Peroxisome Proliferator-Activated Receptor-{gamma} in Thyroid Eye Disease: Contraindication for Thiazolidinedione Use? J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 55 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W Chan, G W K Wong, D S P Fan, A C K Cheng, D S C Lam, and J S K Ng Ophthalmopathy in childhood Graves' disease Br. J. Ophthalmol., July 1, 2002; 86(7): 740 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Valyasevi, D. A. Harteneck, C. M. Dutton, and R. S. Bahn Stimulation of Adipogenesis, Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR{gamma}), and Thyrotropin Receptor by PPAR{gamma} Agonist in Human Orbital Preadipocyte Fibroblasts J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2352 - 2358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Metcalfe, N. Jordan, P. Watson, S. Gullu, M. Wiltshire, M. Crisp, C. Evans, A. Weetman, and M. Ludgate Demonstration of Immunoglobulin G, A, and E Autoantibodies to the Human Thyrotropin Receptor Using Flow Cytometry J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1754 - 1761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pritchard, N. Horst, W. Cruikshank, and T. J. Smith Igs from Patients with Graves' Disease Induce the Expression of T Cell Chemoattractants in Their Fibroblasts J. Immunol., January 15, 2002; 168(2): 942 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Busuttil and A. G. Frauman Extrathyroidal Manifestations of Graves' Disease: The Thyrotropin Receptor Is Expressed in Extraocular, But Not Cardiac, Muscle Tissues J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2315 - 2319. [Abstract] [Full Text]
|
|
|
|
|
|
R. W. Valyasevi, S. C. Jyonouchi, C. M. Dutton, N. Munsakul, and R. S. Bahn Effect of Tumor Necrosis Factor-{{alpha}}, Interferon-{{gamma}}, and Transforming Growth Factor-{beta} on Adipogenesis and Expression of Thyrotropin Receptor in Human Orbital Preadipocyte Fibroblasts J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 903 - 908. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. P. Weetman Graves' Disease N. Engl. J. Med., October 26, 2000; 343(17): 1236 - 1248. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Crisp, K. J. Starkey, C. Lane, J. Ham, and M. Ludgate Adipogenesis in Thyroid Eye Disease Invest. Ophthalmol. Vis. Sci., October 1, 2000; 41(11): 3249 - 3255. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Bell, A. Gagnon, L. Grunder, S. J. Parikh, T. J. Smith, and A. Sorisky Functional TSH receptor in human abdominal preadipocytes and orbital fibroblasts Am J Physiol Cell Physiol, August 1, 2000; 279(2): C335 - C340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bartalena, A. Pinchera, and C. Marcocci Management of Graves' Ophthalmopathy: Reality and Perspectives Endocr. Rev., April 1, 2000; 21(2): 168 - 199. [Abstract] [Full Text]
|
|
|
|
|
|
K. Gunji, A. De Bellis, A. W. Li, M. Yamada, S. Kubota, B. Ackrell, S. Wengrowicz, A. Bellastella, A. Bizzarro, A. Sinisi, et al. Cloning and Characterization of the Novel Thyroid and Eye Muscle Shared Protein G2s: Autoantibodies against G2s Are Closely Associated with Ophthalmopathy in Patients with Graves' Hyperthyroidism J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1641 - 1647. [Abstract] [Full Text]
|
|
|
|
|
|
R. W. Valyasevi, D. Z. Erickson, D. A. Harteneck, C. M. Dutton, A. E. Heufelder, S. C. Jyonouchi, and R. S. Bahn Differentiation of Human Orbital Preadipocyte Fibroblasts Induces Expression of Functional Thyrotropin Receptor J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2557 - 2562. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
