Thyroid stimulating immunoglobulins, like thyrotropin activate both the cyclic AMP and the PIP2 cascades in CHO cells expressing the TSH receptor.
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.
Institute of Interdisciplinary Research, School of Medicine, University of Brussels, Belgium.
J
J
Van Sande
C
C
Lejeune
M
M
Ludgate
D S
DS
Munro
G
G
Vassart
J E
JE
Dumont
J
J
Mockel
D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000502:physiology*; D011989:Receptors, Thyrotropin / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems
D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011989:Receptors, Thyrotropin; D000242:Cyclic AMP