Influences of cholera toxin on thyroid stimulation by thyrotropin and thyroid-stimulating antibody.

ABSTRACT

Thyroid-stimulating antibody (TSAb) is an immunoglobulin G (IgG) occurring in the blood in hyperthyroid Graves' disease patients; it stimulates the thyroid in a manner analogous to the action of TSH, i.e. by activation of adenylate cyclase. Since cholera toxin is also known to stimulate thyroid adenylate cyclase, we studied possible interaction of the enterotoxin on effects of TSAb and TSH using slices of canine thyroid in vitro and an increase in the concentration of cAMP as endpoint. Normal human IgG, known to inhibit the binding of [125I]-iodo-TSH to thyroid membranes, decreased stimulation of thyroid slices by TSH; this inhibitory effect occurred also with preparations of TSAb (inevitably comprised mainly of normal IgG) that were themselves stimulatory. The cholera toxin effect was not prevented by normal IgG and, by factorial analysis of variance, was shown to potentiate the action of subsequently added TSAb or TSH. There was also positive interaction of the effect of TSAb with the combination of TSH and cholera toxin. The data indicate that responses of thyroid tissue to TSAb and TSH are readily influenced by effects of other membrane-active agents (in the present context, normal IgG and cholera toxin).