Susceptibility to proteolysis of thyroglobulin from rats and guinea-pigs treated with excess iodide

The effect of excess iodide on proteolysis of in vivo 125I-labelled thyroglobulin (Tg) from rats and guinea-pigs was investigated in vitro using preparations of thyroid lysosomes and exogenous proteases (Pronase). Lysosomes were obtained by centrifugation of pig thyroid homogenates. This lysosomal preparation induced maximal proteolysis of Tg at pH 3.6 to 4.6 and was stimulated by KCl. Treatment of rats with excess iodide for up to 28 days had no effect on the proteolysis of Tg by lysosomes or Pronase. Decreased resistance of Tg to proteolysis by lysosomes and pronase was observed in guinea-pigs treated with excess iodide for 3 days, whereas Tg from guinea-pigs treated for longer time periods had increased resistance to proteolysis. This difference in the susceptibility to proteolysis of Tg provides an explanation why long-term administration of excess iodide is goitrogenic in guinea-pigs but not in rats.