Interaction between thyroid-stimulating immunoglobulins and thyrotropin receptors in fat cell membranes

In the TSH radioreceptor assay to study the interaction between Graves' immunoglobulins (Ig) and TSH receptors in guinea pig fat cell membranes, Graves' Ig were found to inhibit [125I]TSH binding to fat cell membranes in a dose-dependent manner. Scatchard analysis of [125I]TSH displacement curves by Graves' Ig indicated a single population of the binding sites in fat cell membranes, in contrast to two populations of TSH-binding sites in the membranes. Displacement of [125I]TSH bound to fat cell membranes by both Graves' Ig and unlabeled TSH were time and temperature dependent, with similar dissociation curves, suggesting a specific binding of Graves' Ig to the membrane sites related to the TSH receptor in the fat cells. Such Ig are referred to as fat cell-binding Ig, to be distinguished from the thyroid-stimulating Ig (TSI) detected by TSH radioreceptor assay using human thyroid membranes. Both fat cell-binding Ig and TSI were detected in the sera of a great majority of untreated patients with Graves' disease. A significant correlation was found between both values (r = 0.80; n = 19; P less than 0.001). According to these results, TSI might represent an autoantibody to the membranes associated with the TSH receptor of the target tissues without a strict organ specificity.