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 thyroid autoregulation, however, their occurrence in vivo has not yet been demonstrated. We therefore tried to identify delta-iodolactone (5-Hydroxy-6-iodo-8,11,14-eicosatrienoic delta-lactone, IL-delta) in thyroid tissue from a patient with Graves' disease treated with high doses of iodide. Lipids were extracted from thyroid tissue, purified by reversed phase chromatography and analyzed by gas chromatography--tandem mass spectrometry (GC-MSMS). The retention time in gas chromatography and fragmentation pattern in tandem mass spectrometry were determined with biochemically synthesized non-deuterated and deuterated IL-delta. According to retention time (13.44 min) and specific fragments (m/z 303, m/z 259) the occurrence of IL-delta could be demonstrated in the extract of iodide treated goiter. In vitro, potassium iodide (40 microM) as well as IL-delta (1.0 microM) significantly inhibited the proliferation of human thyroid follicular cells induced by phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate). These results demonstrate for the first time that Il-delta is present in iodide treated human thyroid. As cell proliferation is under negative control of IL-delta, a crucial role in thyroid involution following iodide treatment may be possible.
Dugrillon
A
A
Medizinische Klinik, Universität München, Germany.
Uedelhoven
W M
WM
Pisarev
M A
MA
Bechtner
G
G
Gärtner
R
R
D001095:Arachidonic Acids / Q000032:analysis* / Q000302:isolation & purification; D002455:Cell Division / Q000187:drug effects*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006042:Goiter / Q000188:drug therapy*; D006801:Humans; D066298:In Vitro Techniques; D007454:Iodides / Q000627:therapeutic use*; D013961:Thyroid Gland / Q000166:cytology / Q000254:growth & development*
C026915:6-iodo-5-hydroxy-eicosatrienoic acid, delta-lactone; D001095:Arachidonic Acids; D007454:Iodides