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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 7 2557-2562
Copyright © 1999 by The Endocrine Society

Original Studies

Differentiation of Human Orbital Preadipocyte Fibroblasts Induces Expression of Functional Thyrotropin Receptor1

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

Division of Endocrinology, Mayo Clinic/Foundation (R.W.V., D.Z.E., D.A.H., C.M.D., S.C.J., R.S.B.), Rochester, Minnesota 55905; and Medizinische Klinik, Klinikum Innenstadt, University of Munich (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

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.




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