One Monoclonal Antibody to Human Thyrotropin (TSH) Receptor Agonist of TSH Hormone Stimulates the Proliferation of Human Thyroid Cells

Abstract The question of thyroid cell growth induction by monoclonal antibodies (mAbs) to human thyrotropin receptor (hTSH-R), which stimulate increases in cAMP thyroid cells, is under debate and their implication in Graves' disease (GD) is controversial. In order to address this issue, we used characterized reagents, i.e., mAbs to hTSH-R, and cloned human thyroid hybridoma cells (GEJ). Cell counting on Days 1, 2, and 3 after addition of mAb and Northern blot analysis of mRNA specific for the c-fos oncogene were used to assess the proliferation of the thyroid cells, MAbs to hTSH-R, obtained by immunization of DBA/1 mice with affinity-purified hTSH-R, were added to GEJ cells in concentrations varying from 0.66 to 660 n M . Their effects on GEJ cell growth were compared to those of human TSH, of hLH, and of control mAb. Cell counting and evaluation of GEJ c-fos transcripts showed that mAbs to hTSH-R induce significant GEJ cell growth, whereas they were ineffective on the control cell line. Among them, one mAb, 34A, exhibited an impressive activity on thyroid cell growth and induced cAMP production comparable to that induced by bovine or human TSH. Our data demonstrate the existence of immunoglobulin which stimulates thyroid growth and elevates cAMP. The higher the cAMP production, the greater the thyroid cell proliferation. Furthermore, the data suggest a possible role for agonistic anti-hTSH-R autoantibodies in the immunopathogenesis of GD.