PRESENCE OF NONFUNCTIONAL THYROTROPIN RECEPTOR VARIANT TRANSCRIPTS INRETROOCULAR AND OTHER TISSUES

The TSH receptor (TSHR) has been proposed as an antigenic link between the thyroid and the orbit; TSHR transcripts have been demonstrated by other groups, one in orbital tissue and the other in orbital and derm al fibroblasts. In a previous study we were unable to demonstrate tran scripts for the complete TSHR in retroocular muscle containing also fi broblasts. We now confirm this finding. A 1.3-kilobase variant of the TSHR messenger ribonucleic acid (mRNA) has been described in normal an d Graves' thyroids; it contains exons 1-8 of the major mRNA species an d a unique 3'-sequence predicted to encode further amino acids and a p olyadenylated tail. Lacking the membrane-spanning region, the correspo nding variant protein, if expressed, is not expected to couple to G-pr oteins. Using primers specific for this variant in reverse polymerase chain reaction experiments, Southern blotting and frequencies, we demo nstrate the presence of this transcript in normal and Graves' thyroid, extraocular muscle, peripheral blood mononuclear cells, and, to a les ser extent, in fat and fibroblasts. TSH-mediated protein synthesis, cA MP, and glycosaminoglycan production have been measured in cultured fi broblasts. At 5 mU/mL, bovine TSH stimulated glycosaminoglycan product ion, but recombinant TSH did not, even at higher concentrations, sugge sting that contaminating factors are responsible. Together the data do not support the presence of a functional complete TSHR in orbital tis sue. However, they are compatible with a role for the extracellular po rtion of the receptor as a nonfunctional autoantigen and provide some explanation for the conflicting results with regard to the relevance o f the TSHR in the pathophysiology of thyroid-associated ophthalmopathy .