Adipogenesis and TSH Receptor Expression

  • Natee Munsakul
  • Rebecca S. Bahn
Part of the Endocrine Updates book series (ENDO, volume 14)


The symptoms and signs of Graves’ ophthalmopathy (GO) can be explained mechanically by an increase in the volume of tissues within the confines of the bony orbit. Volume measurements of the orbital adipose/connective tissue compartment and the extraocular muscles using computed tomography (CT) scans revealed abnormalities in 87% of Graves’ patients with clinically detectable GO (1). Enlarged muscles with normal fat volume was noted in 48% of these patients, while enlargement of both the extraocular muscles and the fat compartment was found in 46% of patients. The converse, or increased fat compartment volume with normal muscle volumes, was found in 8% of GO patients. In another study, measurement of extraocular muscle volumes in 50 patients with GO revealed relatively poor correlation between the extent of muscle enlargement and proptosis measurements. In contrast, another group of investigators found the degree of proptosis to correlate well with orbital fat volumes (2). Taken together, these studies suggest that orbital adipose tissue expansion in GO likely influences the degree of proptosis to a greater extent than does the extraocular muscle enlargement.


Adipocyte Differentiation Extraocular Muscle Stromal Vascular Fraction Thyrotropin Receptor Orbital Fibroblast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Forbes G, Gorman CA, Brennan MD, Gehring DG, Ilstrup DM, Earnest F. 1986 Ophthalmopathy of Graves’ disease: computerized volume measurements of the orbital fat and muscle. Am J Neuroradiol. 7:651–656.PubMedGoogle Scholar
  2. 2.
    Peyster RG, Ginsberg F, Silber JH, Adler LP. 1986 Exophthalmos caused by excessive fat: CT volumetric analysis and differential diagnosis. Am J Neuroradiol. 7:35–40.Google Scholar
  3. 3.
    Campbell RJ. 1984 Pathology of Graves’ ophthalmopathy: IN: Gorman CA, Waller RA, Dyer JA (eds): The Eye and Orbit in Thyroid Disease. New York Raven, pp.25–31.Google Scholar
  4. 4.
    Tallstedt L Norberg R. 1988 Immunohistochemical staining of normal and Graves’ extraocular muscle. Invest Ophthalmol Vis Sci. 29:175–184.PubMedGoogle Scholar
  5. 5.
    Sorisky A.1999 From preadipocyte to adipocyte: differentiation-directed signals of insulin from the cell surface to the nucleus. Crit Rev Clin Lab Sci. 36(1):1–34.PubMedCrossRefGoogle Scholar
  6. 6.
    Poznanski W, Waheed I, Van R. 1973 Human fat cell precursors. Morphologic and metabolic differentiation in culture. J Lab Invest. 29:570–576.Google Scholar
  7. 7.
    Smas CM, Sul HS. 1995 Control of adipocyte differentiation. Biochem. 309:697–710.Google Scholar
  8. 8.
    Gimble JM, Robinson CE, Clarke SL, Hill MR. 1998 Nuclear hormone receptors and adipogenesis. Crit Rev Eukaryot Gene Expr. 8(2):141–168.PubMedCrossRefGoogle Scholar
  9. 9.
    Hirsch J, Fried SK, Edens NK,Leibel RL. 1989 The fat cell. Med Clin N Am. 73:83–96.Google Scholar
  10. 10.
    Alihaud G, Grimaldi P, Negrel R. 1994 Hormonal regulation of adipose differentiation. Trends Endocrinol Metab. 5:132–136.CrossRefGoogle Scholar
  11. 11.
    Shillabeer G, Forden JM, Lau DCW. 1989 Induction of preadipocyte differentiation by mature fat cells in the rat. J Clin Invest. 84:381–387.PubMedCrossRefGoogle Scholar
  12. 12.
    Green H, Kehinde O. 1975 An established preadipose cell line and its differentiation in culture. Factors affecting adipose conversion. Cell. 5:19–27.PubMedCrossRefGoogle Scholar
  13. 13.
    Green H, Kehinde O. 1976 Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells. Cell. 7:105–113.PubMedCrossRefGoogle Scholar
  14. 14.
    Negral R, Grimaldi P, Alihaud G. 1978 Establishment of a proadipocyte clonal line from epididymal fat pad of ob/ob mouse that responds to insulin and to lipolytic hormones. Proc Natl Acad Sci USA. 75:6054–6058.CrossRefGoogle Scholar
  15. 15.
    Cowherd RM, Lyle RE, McGehee Jr RE.1999 Molecular regulation of adipocyte differentiation. Semin Cell Dev Biol. 10:3–10.PubMedCrossRefGoogle Scholar
  16. 16.
    Sorisky A, Pardasani D, Gagnon A, Smith Ti. 1996 Evidence of adipocyte differentiation in human orbital fibroblasts in primary culture. J Clin Endocrinol Metab. 81:3428–3431.PubMedCrossRefGoogle Scholar
  17. 17.
    Hauner H, Entenmann G, Wabitsch M, Gaillard D, Alihaud G, Negerl R, Pfeiffer EF. 1989 Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest. 84:1663–1670.PubMedCrossRefGoogle Scholar
  18. 18.
    Cornelius P, MacDougald OA, Lane MD. 1994 Regulation of adipocyte development. Annu Rev Nutr. 14:99–129.PubMedCrossRefGoogle Scholar
  19. 19.
    Gregoire FM, Smas CM, Sul HS. 1998 Understanding adipocyte differentiation. Physiol Rev. 78:738–809.Google Scholar
  20. 20.
    Smas CM, Sul HS. 1993 Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation.Cell 73: 725–734.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhou YT, Wang ZW, Higa M, Newgard CB, Unger RH. 1999 Reversing adipocyte differentiation: implications for treatment of obesity. Proc Natl Acad Sci USA. 96:2391–2395.PubMedCrossRefGoogle Scholar
  22. 22.
    Rodbell M. 1964 Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 239: 375–380.PubMedGoogle Scholar
  23. 23.
    Davies TF, Teng CS, McLachlan SM, Smith BR, Hall R. 1978 Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes. Molecular and Cellular Endocrinology 9: 303–310.PubMedCrossRefGoogle Scholar
  24. 24.
    Perros P, Kendall-Taylor P. 1994 Demonstration of thyrotropin binding sites in orbital connective tissue: Possible role in the pathogenesis of thyroid-associated ophthalmopathy. J Endocrinol Invest 17: 163–170.PubMedGoogle Scholar
  25. 25.
    Kendall-Taylor P, Munro DS. 1971 The lipolytic activity of long-acting thyroid stimulator. Biochem Biophys Acta 231: 314–319.PubMedCrossRefGoogle Scholar
  26. 26.
    Roselli-Rehfuss L, Robbins LS, Cone RD. 1992 Thyrotropin receptor messenger ribonucleic acid is expressed in most brown and white adipose tissues in the guinea pig. Endocrinol 130: 1857–1861.CrossRefGoogle Scholar
  27. 27.
    Haraguchi K, Shimura H, Ling L, Saito T, Endo T, Onaya T. 1996 Differentiation of rat preadipocytes is accompanied by expression of thyrotropin receptor. Endocringology 137: 3200–3205.CrossRefGoogle Scholar
  28. 28.
    Mullin BR, Lee G, Ledley FD, Winand RJ, Kohn LD. 1976 Thyrotropin interactions with human fat cell membrane preparations and the finding of a soluble thyrotropin binding component. Biochemical and Biophysical Research Communications 69:55–62.PubMedCrossRefGoogle Scholar
  29. 29.
    Marcus C, Ehren H, Bolme P, Amer P. 1988 Regulation of lipolysis during the neonatal period: Importance of thyrotropin. J Clin Invest 82: 1793–1797.PubMedCrossRefGoogle Scholar
  30. 30.
    Janssen A, Karlsson FA, Micha- Johansson G, Bolme P, Bronnegard M, Marcus C. 1995 Effects of stimulatory and inhibitory thyrotropin receptor antibodies on lipolysis in infant adipocytes. J Clin Endocrinol Metab 80: 1712–1716.CrossRefGoogle Scholar
  31. 31.
    Valyasevi RW, Erickson DZ, Harteneck DA, et al. 1999 Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. J Clin Endocrinol Metab 84: 2557–2562.PubMedCrossRefGoogle Scholar
  32. 32.
    Erickson DZ, Harteneck DA, Erickson BJ, Dutton CM, Bahn RS. Induction of leptin expression in orbital preadipocyte fibroblasts. Thyroid, in press.Google Scholar
  33. 33.
    Heufelder AE, Dutton CM, Sarkar G, Donovan KA, Bahn RS. 1993 Detection of TSH receptor RNA in cultured fibroblasts from patients with Graves’ ophthalmopathy and pretibial dermopathy. Thyroid. 3:297–300.PubMedCrossRefGoogle Scholar
  34. 34.
    Feliciello A, Porcellini A, Ciullo, Bonavolonta G, Avvedimento EV, Fenzi G. 1993 Expression of thyrotropin-receptor mRNA in healthy and Graves’ retro-orbital tissue. Lancet 342:337–338.PubMedCrossRefGoogle Scholar
  35. 35.
    Mengistu M, Lukes YG, Nagy EV, Burch FIB, Carr FE, Lahiri S, Burman KD. 1994 TSH receptor gene expression in retroocular fibroblasts. J Endocrinol Invest. 17:437–441.PubMedGoogle Scholar
  36. 36.
    Bahn RS, Dutton CM, Natt N, Joba W, Spitzweg C, Heufelder AE. Thyrotropin receptor expression in Graves’ orbital adipose/connective tissues: potential autoantigen in Graves’ ophthalmopathy. J Clin Endocrinol Metab 83:998–1002, 1998.PubMedCrossRefGoogle Scholar
  37. 37.
    Bahn RS, Heufelder AE. 1993 Pathogenesis of Graves’ ophthalmopathy. N Engl J Med. 329:1468–1475.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Natee Munsakul
    • 1
  • Rebecca S. Bahn
    • 1
  1. 1.Division of EndocrinologyMetabolism and Nutrition, Mayo Clinic/FoundationRochester

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