Graves' immunoglobulin G stimulates iodide efflux in FRTL-5 thyroid cells.
TSH induced I- efflux in FRTL-5 cells, a cell line derived from normal rat thyroid cells, is not mediated by cAMP but intracellular Ca2+ signaling. Graves' patient immunoglobulin G is known to activate the thyroidal cAMP pathway, but little is known about the activation of Ca2+ signaling. We report here that, similarly to TSH, the polyethylenglycol-precipitated serum fraction of Graves' patients induces I- efflux in FRTL-5 cells. The cells grown in the presence of TSH were incubated for 3 weeks in a Ham's 10 medium containing 1% CS, insulin, and hydrocortison for TSH depletion. After preincubating with 125I-iodide for 50 min to label intracellular iodide, the cells were challenged by serum samples for 1 min. The addition of normal pooled-serum hardly affected the I- efflux. The Graves' immunoglobulin G fractions dose-dependently stimulated I- efflux. The averaged potency of 12 patients' sera relative to the values of the pooled serum as 100% was 217 +/- 56.4%. This value was significantly higher (P < 0.001) than that for eight normal subjects (110 +/- 16.1%). The present study is the demonstration suggesting that Graves' thyrotoxicosis is mediated not only by an adenylate cyclase-cAMP system but also by a phospholipid-Ca2+ system.
Shoda
Y
Y
First Department of Internal Medicine, Gunma University, Maebashi, Japan.
Kondo
Y
Y
Kobayashi
I
I
D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D007454:Iodides / Q000378:metabolism*; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology
D001323:Autoantibodies; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D007454:Iodides; D013972:Thyrotropin; D000242:Cyclic AMP; D002118:Calcium