Hormonal regulation of hyaluronate synthesis in cultured human fibroblasts: evidence for differences between retroocular and dermal fibroblasts.
Fibroblasts derived from retroocular connective tissue and skin were propagated in culture in an effort to identify structural and functional differences in connective tissue which might explain the apparent region-specific involvement in Graves' disease. Striking morphological differences existed between cultured cells from the two anatomical sites. Inhibition of glycosaminoglycan (GAG) accumulation by T3 and dexamethasone in these cultures was compared. Confluent cultures were labeled with [3H]acetate, and total [3H]GAG was quantitated. Fibroblasts from the skin responded to T3 (100 nmol/L) and dexamethasone (100 nmol/L) with 27% and 55% inhibition of [3H]GAG accumulation, respectively (n = 12). In contrast, retroocular fibroblasts responded with 12% and 8% inhibition (n = 6) to the two hormones. When cultures from abdominal skin and retroocular tissue were treated with n-butyrate (10 mM), a compound known to inhibit hyaluronate specifically, they responded similarly with 78% and 83% inhibition, respectively. A pulse-chase study was performed using fibroblasts from both sites, and no [3H]GAG degradation could be detected for the duration of the chase period (up to 72 h). These results suggest that retroocular fibroblasts, likely participants in the pathogenesis of Graves' ophthalmopathy, do not respond vigorously to T3 or glucocorticoids in terms of inhibition of [3H]GAG synthesis as do their dermal counterparts.
Smith
T J
TJ
Department of Medicine, State University of New York, School of Medicine and Biomedical Sciences, Buffalo 14215.
Bahn
R S
RS
Gorman
C A
CA
D002478:Cells, Cultured; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005123:Eye / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006111:Graves Disease / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*
D006025:Glycosaminoglycans; D014284:Triiodothyronine; D003907:Dexamethasone; D006820:Hyaluronic Acid