Thyroid stimulating immunoglobulins, like thyrotropin activate both the cyclic AMP and the PIP2 cascades in CHO cells expressing the TSH receptor
J Van Sande, C Lejeune, M Ludgate, DS Munro… - Molecular and cellular …, 1992 - Elsevier
J Van Sande, C Lejeune, M Ludgate, DS Munro, G Vassart, JE Dumont, J Mockel
Molecular and cellular endocrinology, 1992•ElsevierIn 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 …
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 …
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 (PIP2) 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 PIP2 hydrolysis in human thyroid slices. We show in this study that TSAb are able to activate the PIP2 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.
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