Differentiation of Human Orbital Preadipocyte Fibroblasts Induces Expression of Functional Thyrotropin Receptor1
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...
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Published in | The journal of clinical endocrinology and metabolism Vol. 84; no. 7; pp. 2557 - 2562 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Endocrine Society
01.07.1999
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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. |
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AbstractList | 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. 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. |
Author | Bahn, Rebecca S Dutton, Charyl M Heufelder, Armin E Harteneck, Debra A Jyonouchi, Soma C Erickson, Dana Z Valyasevi, Rosanee W |
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Cites_doi | 10.1530/eje.0.1360599 10.1016/S0006-291X(76)80271-9 10.1016/0303-7207(78)90072-2 10.1172/JCI113793 10.1016/0006-291X(90)90789-P 10.1016/S0161-6420(84)34152-5 10.1210/endo.137.8.8754740 10.1056/NEJM199311113292007 10.1016/S0022-2275(20)38656-9 10.1089/thy.1993.3.297 10.1007/BF03347732 10.1007/BF03347708 10.1016/0006-291X(89)92727-7 10.1016/0140-6736(93)91475-2 10.2527/1998.76148x 10.1016/S0167-4889(97)00083-9 10.1089/thy.1998.8.411 10.1210/jcem-65-4-665 |
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References | (2020071621583721200_R20) 1964; 239 Mengistu (2020071621583721200_R12) 1994; 17 Roselli-Rehfuss (2020071621583721200_R23) 1992; 130 Hausman (2020071621583721200_R6) 1998; 76 Spitzweg (2020071621583721200_R15) 1997; 136 Heufelder (2020071621583721200_R10) 1993; 3 Bahn (2020071621583721200_R8) 1993; 329 Wiederer (2020071621583721200_R5) 1987; 28 Feliciello (2020071621583721200_R11) 1993; 342 Davies (2020071621583721200_R21) 1978; 9 Peyster (2020071621583721200_R2) 1986; 7 Ludgate (2020071621583721200_R13) 1998; 8 Marcus (2020071621583721200_R26) 1988; 82 Nagayama (2020071621583721200_R17) 1989; 165 Perros (2020071621583721200_R22) 1994; 17 Sorisky (2020071621583721200_R7) 1996; 81 Bahn (2020071621583721200_R9) 1998; 83 Forbes (2020071621583721200_R1) 1986; 7 Haraguchi (2020071621583721200_R24) 1996; 137 Burch (2020071621583721200_R14); 78 Perret (2020071621583721200_R16) 1990; 171 Mullin (2020071621583721200_R25) 1976; 69 Strutt (2020071621583721200_R19) 1996; 2 Bahn (2020071621583721200_R18) 1987; 54 Hufnagel (2020071621583721200_R3) 1984; 91 Chen (2020071621583721200_R4) 1997; 1359 |
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Snippet | Although the autoantigen involved in Graves’ hyperthyroidism is known
to be the TSH receptor (TSHr), whether this antigen plays a primary
role in the... Although the autoantigen involved in Graves’ hyperthyroidism is known to be the TSH receptor (TSHr), whether this antigen plays a primary role in the... |
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Title | Differentiation of Human Orbital Preadipocyte Fibroblasts Induces Expression of Functional Thyrotropin Receptor1 |
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