IDENTIFICATION OF DELTA-IODOLACTONE IN IODIDE TREATED HUMAN GOITER AND ITS INHIBITORY EFFECT ON PROLIFERATION OF HUMAN THYROID-FOLLICLES

There is evidence that iodoarachidonates are mediators of iodide in th yroid autoregulation, however, their occurrence in vivo has not yet be en demonstrated. We therefore tried to identify delta-iodolactone (5-H ydroxy-6-iodo-8,11,14-eicosatrienoic delta-lactone, IL-delta) in thyro id tissue from a patient with Graves' disease treated with high doses of iodide. Lipids were extracted from thyroid tissue, purified by reve rsed phase chromatography and analyzed by gas chromatography - tandem mass spectrometry (GC-MSMS). The retention time in gas chromatography and fragmentation pat tern in tandem mass spectrometry were determined with biochemically synthesized non-deuterated and deuterated IL-delta . According to retention time (13.44 min) and specific frag- ments (m/ z 303, m/z 259) the occurrence of IL-delta could be demonstrated in th e extract of iodide treated goiter. In vitro, potassium iodide (40 mu M) as well as IL-delta (1.0 mu M) significantly inhibited the prolifer ation of human thyroid follicular cells induced by phorbol ester TPA ( 12-O-tetradecanoylphorbol 13-acetate). These results demonstrate for t he first time that Il-delta is present in iodide treated human thyroid . As cell proliferation is under negative control of IL-delta, a cruci al role in thyroid involution following iodide treatment may be possib le.