Inhibition of long-acting thyroid stimulator by thyroid particulate fractions.

Abstract

The long acting thyroid stimulator (LATS) of Graves disease is probably an Immunoglobulin G; therefore, LATS may be an antibody. To test this hypothesis, fractions of thyroid tissue were incubated with serum containing the long-acting stimulator to discover whether any interaction occurred. All subcellular fractions of thyroid tissue reduced LATS activity, but the microsomal fraction contained a potent, consistent inhibitor whose effectivity is proportionate to its quantity. This inhibitor is stable at 4[degree] C, heat-labile and resistant to ribonuclease and several inhibitors of enzymatic activity. Microsomal fractions isolated from 6 non thyroidal tissues did not inhibit LATS; inhibitory activity could not be satisfactorily extracted into protein-containing solutions but not into physiological saline. Thyrotropin was inhibited by incubation with thyroid microsomes, but small amounts of thyroxine also decreased thyrotropin effect in the bioassay system; a direct interaction of thyroid microsomes and thyrotropin was therefore not established. LATS was not inhibited by any amount of thyroxine below 100 [mu]g/mouse. Although the thyroid microsomal fractions contained acid hydrolases, like those found in lysosomes, the presence of such enzymes did not correlate with inhibition of LATS. However, LATS was recovered repeatedly from acidic extracts of microsomes that had previously been incubated with serum containing LATS, sedimented, and washed in normal serum. These observations are presented to support the hypothesis that LATS is an antibody reacting with an antigen in the thyroid microsomal fraction.