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
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.