THYROTROPIN RECEPTOR EXPRESSION IN GRAVES ORBITAL ADIPOSE CONNECTIVE TISSUES - POTENTIAL AUTOANTIGEN IN GRAVES OPHTHALMOPATHY/

It is acknowledged that the TSH receptor (TSHr) on thyroid follicular cells is the autoantigen involved in the hyperthyroidism of Graves' di sease. However, whether this receptor is expressed in extrathyroidal t issues, and whether it participates directly in the pathogenesis of Gr aves' ophthalmopathy (GO) are unclear. We sought to detect the express ion of TSHr messenger ribonucleic acid (mRNA) and protein in orbital a dipose/connective tissue specimens and in human orbital preadipocyte f ibroblast cultures using liquid hybridization analysis and immunohisto chemical methods. We demonstrated intact and variant TSHr mRNA transcr ipts and TSHr-like immunoreactivity in orbital adipose/connective tiss ue specimens from patients with GO. In addition, TSHr-like immunoreact ivity was detected in early passage GO preadipocyte fibroblast culture s that were shown to include some adipose cells. In contrast, neither TSHr mRNA nor protein was detected in normal orbital adipose/connectiv e tissue specimens or in late passage GO orbital fibroblast cultures c ontaining no lipid-laden adipose cells. In conclusion, we showed that TSHr is expressed in the adipose/ connective tissue of the diseased or bit in GO. In addition, TSHr is demonstrable in early passage GO pread ipocyte orbital fibroblast cultures that contain a subpopulation of ad ipocytes. Subsequent passaging of these cells results in the loss of b oth TSHr expression and adipocyte-specific staining. These results sug gest that both the expression of this receptor and the accumulation of adipose tissue in the orbit in GO mag be induced in vivo by a humoral factor(s) not present in the fell culture environment.