Identification of δ-Iodolactone in Iodide Treated Human Goiter and its Inhibitory Effect on Proliferation of Human Thyroid Follicles

Abstract

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.

Antineoplastic effect of iodine and iodide in dimethylbenz[a]anthracene-induced mammary tumors: association between lactoperoxidase and estrogen-adduct production

“…In the first case, more than one mechanism or iodine component may be triggered or generated by the iodine/iodide supplement. Several groups have postulated that the antineoplastic I 2 effect could be mediated by direct antioxidant/oxidant action at the mitochondrial level or by the formation of iodolipid intermediates such as 6-IL or iodohexadecanal (Dugrillon et al 1994, Shrivastava et al 2006, Rosner et al 2010. Our group has demonstrated that 6-IL formation in solid tumors (MNU) or cancerous cells (MCF-7) is associated with elevated concentrations of its precursor AA, and that 6-IL formation is independent of peroxidases when the supplement is I 2 (Arroyo- Helguera et al 2006).…”

Role of Transforming Growth Factor Beta in the Regulation of Thyroid Function and Growth

“…In porcine monolayer cultures, organified iodine stimulated both TGF-b1 mRNA and protein (23). In porcine follicles in suspension TGF-b1 mRNA expression was increased by epidermal growth factor (EGF) and TGF-a, and these actions were slightly decreased by the simultaneous addition or either iodide or 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid delta lactone (d-iodolactone, one of the iodocompounds proposed to be involved in thyroid autoregulation) (20,24). Under similar conditions, TSH and forskolin decreased this parameter, and this effect was reversed by iodide or d-iodolactone.…”

Signaling pathways involved in the antiproliferative effect of molecular iodine in normal and tumoral breast cells: evidence that 6-iodolactone mediates apoptotic effects

“…It has been suggested that in thyroid gland the apoptotic iodide (I K ) effect is mediated by the derivatives of arachidonic acid (AA) or eicosapentaenoic acid such as 6-iodolactone (6-IL) or a-iodohexadecanal respectively (Dugrillon et al 1994, Langer et al 2003. The formation of these iodolipids requires, in addition to iodide uptake by specific transporters, its oxidation by thyroperoxidase (Shah et al 1986, Dohan et al 2003.…”