TSH receptor in endocrine autoimmunity

The human thyrotropin receptor (hTSHR) is a potential common antigen in endocrine autoimmunity. Recently, some studies demonstrated transcripts for hTSHR or its components in the extrathyroidal tissue of patients with autoimmune thyroid disease (ATD), although others were unable to confirm these findings. In the present study we investigated orbital adipose/connective and muscle tissue as well as primary cell cultures of orbital fibroblasts and myoblasts from patients with thyroid and eye disease.

The messenger ribonucleic acid (mRNA) of hTSHR was reverse transcribed and amplified by polymerase chain reaction (PCR). To evaluate the existence of a functional hTSHR in cultured orbital fibroblasts and muscle cells, the TSH-mediated metabolic activity of the cells was measured by tetrazolium assay.

We were unable to amplify the extracellular domain of hTSHR regardless of the material used. In contrast, transcripts of the transmembrane and intracellular domain of hTSHR were detectable in both crude retrobulbar tissue and primary cells cultures. The results of fibroblast amplification experiments were more successful than those with myoblasts. Furthermore, we were able to confirm that these transcripts of hTSHR can also be detected in the retro-ocular tissue of healthy persons. Independently of the TSH activity employed, no stimulation of fibroblasts or myoblasts was detected, even at higher TSH levels.

These data do not suggest that hTSHR is expressed in a functional form in orbital tissue. However, a part of the receptor could play a role in the pathogenesis of autoimmune eye disease as a non-functional but antigenic protein. Whether a common antigen in the thyroid and orbit is related to hTSHR has not been clarified yet.