Evidence that thyroid growth autoregulation is mediated by an iodolactone

For further investigating the mechanism of the known autoregulation of thyroid follicle growth and function by iodine, we tried to detect iodolactone (6-iodo-8,11,14-eicosatrienoic-delta-lactone) in isolated porcine thyroid follicles and investigated the effects of in vitro synthesized iodolactone on EGF induced thyroid cell proliferation as well as on TSH induced cycli AMP formation. In vitro synthesis of iodolactone was performed with lactoperoxidase catalyzed iodination of arachidonic acid. With gas chromatography-mass spectrometry a molecular mass of 391 m/z corresponding to the derivatization product of iodolactone was found. An ethanol/chloroform extract of isolated thyroid follicles preincubated with KI (10uM) and arachidonic acid (1uM) revealed an identical substrate. This indicates the ability of thyroid follicles to form iodolactone. Iodolactone (0.1-1.0 uM) dose-dependently inhibited EGF induced thyroid cell growth. This growth inhibiting effect of iodolactone was found to be 50-fold more pronounced than the inhibitory effect of KI (4 x 10(-5] on thyroid cell proliferation. In contrast to the effect of iodide, the inhibitory effect of iodolactone on thyroid cell growth could not be abolished by methimazole (1mM). The basal as well as TSH (0.5 U/l) induced cyclic AMP formation was not changed by iodolactone. These experiments suggest a physiological role of iodolactone as a mediator of the known inhibitory effect of iodide on thyroid growth.