TSH receptor binding and thyroid stimulation by sera from patients with Graves' disease

An investigation of the ability of TSH receptor antibodies to bind to the TSH receptor and stimulate thyroid function is described. Binding studies were carried out using 125I-labelled TSH and detergent solubilised porcine TSH receptors, and the parameter of thyroid stimulation employed was 125I-organification in isolated porcine thyroid cells. Different Graves' sera were found to show different dose-response relationships and three types of antibody activity were evident in the six samples studied. In two samples receptor binding and thyroid stimulating activities were approximately parallel. In two receptor binding was detectable at lower doses than stimulation while in the last two stimulation was detectable at lower doses than binding. It is proposed that these characteristics are due to different populations of receptor antibodies which exhibit different degrees of TSH agonism. Furthermore one of the reasons for the relatively poor correlation between TSH receptor binding and thyroid stimulation observed in series of individual Graves' sera may be the presence of different populations of antibodies showing different dose-response relationships with regard to binding and stimulation.