EXPRESSION LEVELS OF THE THYROTROPIN RECEPTOR GENE IN AUTOIMMUNE THYROID-DISEASE - COREGULATION WITH PARAMETERS OF THYROID-FUNCTION AND INVERSE RELATION TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASSE-I AND CLASSE-II

Using a human TSH receptor (TSH-R) cDNA probe, we investigated TSH-R t ranscript levels in 13 human thyroid fragments by Northern blot analys is; 7 Graves' disease, 2 Hashimoto's disease, 3 endemic goiter, and 1 healthy thyroid gland were studied. TSH-R expression levels were varia ble, but displayed a close correlation to the expression of thyroid pe roxidase (r = 0.703; P < 0.05), thyroglobulin (r = 0.817; P < 0.01), a nd the nuclear oncogene c-fos (r = 0.935; P < 0.001), but not c-myc. O verall, TSH-R transcript levels were low or absent in those thyroids i n which expression of the major histocompatibility complex class I or II (MHC I or II) was high, thus establishing an inverse relation (MHC I, r = -0.791; P < 0.01; MHC II, r = -0.784; P < 0.01). In situ hybrid ization showed that apart from lymphocytes, thyroid cells themselves w ere the source of MHC II transcripts. Gamma-Interferon expression was only detectable in 1 Hashimoto's goiter. Our findings suggest that nex t to lymphocyte infiltration, active regulatory events in the thyrocyt e are responsible for the inverse relation between functional paramete rs (TSH-R, thyroid peroxidase, thyroglobulin, and c-fos) and immunolog ical markers (MHC I and II).