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.