CYCLOOXYGENASE-DEPENDENT THYROID-CELL PROLIFERATION INDUCED BY IMMUNOGLOBULINS FROM PATIENTS WITH GRAVES-DISEASE

Citation
R. Dipaola et al., CYCLOOXYGENASE-DEPENDENT THYROID-CELL PROLIFERATION INDUCED BY IMMUNOGLOBULINS FROM PATIENTS WITH GRAVES-DISEASE, The Journal of clinical endocrinology and metabolism, 82(2), 1997, pp. 670-673
Citations number
26
Categorie Soggetti
Endocrynology & Metabolism
ISSN journal
0021972X
Volume
82
Issue
2
Year of publication
1997
Pages
670 - 673
Database
ISI
SICI code
0021-972X(1997)82:2<670:CTPIBI>2.0.ZU;2-1
Abstract
IgG associated with Graves' disease bind to the TSH receptor and alter thyroid growth and function, mainly through the stimulation of adenyl yl cyclase. In addition, Graves' IgG are able to interact with the pho spholipase C (PLC)/Ca2+ and phospholipase A(2) (PLA(2))/arachidonic ac id (AA) cascades. The activation of this latter pathway leads to thyro id cell growth in vitro. The elucidation of additional mechanisms of a ction of Graves' IgG has made possible the identification of four subg roups of patients, characterized by IgG with different biochemical act ivities (extent of cAMP and AA release stimulation in in vitro assays) . On the basis of these results, a novel therapeutic approach could be proposed based on the inhibition of PLA(2) and AA metabolism. To test this hypothesis, the ability of IgG from 56 Graves' patients to stimu late [[H-3]thymidine incorporation in FRTL5 thyroid cells in the prese nce and absence of the cyclooxygenase inhibitor indomethacin (2.5 x 10 (-6) mol/L) was measured. A significant reduction in [H-3]thymidine in corporation was found (33% inhibition; P < 0.0001) upon pretreatment w ith indomethacin, suggesting that in vitro thyroid cell growth is regu lated by cyclooxygenase metabolites. This strengthens the argument for involvement of the PLA,IAA cascade in the pathophysiology of Graves' disease and the proposal for novel selective pharmacological treatment s of these patients.