The TSH receptor reveals itself

The thyrotropin receptor (TSHR), one of the primary antigens in autoimmune thyroid disease, is a target of both antigen-specific T cells and antibodies in patients with this condition (1). Autoantibodies to the TSHR (TSHR-Ab) act as thyroid stimulating factor (TSH) agonists in autoimmune hyperthyroidism (Robert Graves disease) but as TSH antagonists in autoimmune hypothyroidism (Hashimoto thyroiditis). The TSHR antigen is primarily expressed in the epithelial cells of the thyroid follicles, but TSHR mRNA and protein have been reported in a variety of cell types, some of which show evidence of receptor activity (Table ​(Table11). Table 1 Tissue distribution of the TSHR The TSHR gene, cloned in 1989 (2–5), maps to human chromosome 14q and encodes a predicted seven-transmembrane, G protein–coupled glycoprotein. Although it is similar to the luteinizing hormone receptor and the follicle-stimulating hormone receptor, the TSHR is the largest of the glycoprotein hormone receptors, due primarily to 8– and 50–amino acid insertions in its ectodomain (residues 38–45 and 317–367) (6). As predicted from its cDNA, the TSHR has an unglycosylated molecular weight of 84 kDa but the glycosylated holoreceptor runs on SDS-PAGE with an apparent molecular weight of 95–100 kDa. There are six potential N-linked glycosylation sites on the TSHR, and it was recently shown that the TSHR is also palmitoylated (7). The minimal 5′ promoter region required to confer thyroid-specific expression and cAMP autoregulation extends from 220 to 39 bp upstream of the transcription start site, but there are multiple transcription start sites between –89 and –68 bp (8).