Production of immunoreactive thyroglobulin C-terminal fragments during thyroid hormone synthesis

Here, we studied the fragmentation of the prothyroid hormone, ehyroglobulin (Tg), which occurs during thyroid hormone synthesis, a process which invol ves iodide, thyroperoxidase, and the H2O2-generating system, consisting of glucose and glucose oxidase. Various peptides were found to be immunoreacti ve to autoantibodies to Tg from patients and monoclonal antibodies directed against the immunodominant region of Tg. The smallest peptide (40 kDa) bor e thyroid hormones and was identified at the C-terminal end of the Tg molec ule, which shows homologies with acetylcholinesterase. Similar peptides wer e obtained by performing metal-mediated oxidation of Tg via a Fenton reacti on. It was concluded that the oxidative stress induced during hormone synth esis generates free radicals, which, in turn, cleave Tg into immunoreactive peptides.