Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor

Rosanee W. Valyasevi, Dana Z. Erickson, Debra A. Harteneck, Charyl M. Dutton, Armin E. Heufelder, Soma C. Jyonouchi, Rebecca S. Bahn

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Although the autoantigen involved in Graves' hyperthyroidism is known to be the TSH receptor (TSHr), whether this antigen plays a primary role in the pathogenesis of Graves' ophthalmopathy (GO) is unclear. We sought to determine whether fibroblasts derived from orbital adipose/connective tissue are capable of differentiating into adipocytes that bear immunoreactive and functional TSHr. In addition, we assessed relative levels of TSHr gene expression in normal and GO orbital adipose/connective tissue specimens. GO and normal orbital preadipocyte fibroblasts, cultured under conditions known to stimulate adipocyte differentiation, showed evidence of adipogenesis and positive immunostaining for TSHr protein. In addition, significantly more cAMP was produced in response to TSH stimulation in the differentiated cultures than in undifferentiated cultures derived from the same individuals' cells. Other studies demonstrated relatively greater TSHr gene expression in GO than in normal orbital tissue specimens. These results indicate that orbital preadipocyte fibroblasts increase their TSHr expression with differentiation and suggest that these cells play an important role in the pathogenesis of GO. Furthermore, our studies support the concept that TSHr may be an important target antigen in this condition. Factors that stimulate adipocyte differentiation and TSHr expression in the orbit in GO have yet to be defined.

Original languageEnglish (US)
Pages (from-to)2257-2562
Number of pages306
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number7
StatePublished - 1999

Fingerprint

Thyrotropin Receptors
Fibroblasts
Graves Ophthalmopathy
Adipocytes
Tissue
Gene expression
Connective Tissue
Adipose Tissue
Gene Expression
Antigens
Adipogenesis
Autoantigens
Orbit
Hyperthyroidism
Cell Differentiation
Orbits

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Valyasevi, R. W., Erickson, D. Z., Harteneck, D. A., Dutton, C. M., Heufelder, A. E., Jyonouchi, S. C., & Bahn, R. S. (1999). Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. Journal of Clinical Endocrinology and Metabolism, 84(7), 2257-2562.

Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. / Valyasevi, Rosanee W.; Erickson, Dana Z.; Harteneck, Debra A.; Dutton, Charyl M.; Heufelder, Armin E.; Jyonouchi, Soma C.; Bahn, Rebecca S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 84, No. 7, 1999, p. 2257-2562.

Research output: Contribution to journalArticle

Valyasevi, RW, Erickson, DZ, Harteneck, DA, Dutton, CM, Heufelder, AE, Jyonouchi, SC & Bahn, RS 1999, 'Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor', Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 7, pp. 2257-2562.
Valyasevi RW, Erickson DZ, Harteneck DA, Dutton CM, Heufelder AE, Jyonouchi SC et al. Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. Journal of Clinical Endocrinology and Metabolism. 1999;84(7):2257-2562.
Valyasevi, Rosanee W. ; Erickson, Dana Z. ; Harteneck, Debra A. ; Dutton, Charyl M. ; Heufelder, Armin E. ; Jyonouchi, Soma C. ; Bahn, Rebecca S. / Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. In: Journal of Clinical Endocrinology and Metabolism. 1999 ; Vol. 84, No. 7. pp. 2257-2562.
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