Thyroid stimulating immunoglobulins, like thyrotropin activate both the cyclic AMP and the PIP 2 cascades in CHO cells expressing the TSH receptor

Abstract

In human thyrocytes and in a permanent CHO cell line expressing the human thyroid stimulating hormone (TSH) receptor cDNA (JP09 cells), TSH activates both the cyclic AMP and the phosphatidylinositol 4, 5-bisphosphate (PIP 2) cascade, although the latter effect requires higher TSH concentrations. Thyroid stimulating autoantibodies (TSAb) activate also the human thyroid leading to the hyperthyroidism of Graves' disease. They bind to the TSH receptor and mimic the TSH stimulation of the gland by increasing intracellular cyclic AMP, but they do not enhance PIP 2 hydrolysis in human thyroid slices. We show in this study that TSAb are able to activate the PIP 2 cascade in JP09 cells, a cell line expressing high levels of TSH receptor. This suggests that the mechanism of action of TSAb on the TSH receptor is qualitatively similar to that of TSH.