EVIDENCE THAT IODOLACTONES ARE THE MEDIATORS OF GROWTH-INHIBITION BY IODINE ON THE THYROID

Different iodolipids have been identified within the last decades in t hyroid cells exposed to iodine in vitro as well as in vivo. Iodolipids have been supposed to be involved in thyroid autoregulation, but no s pecific compounds could be found. A new approach was stimulated by the finding that rat thyroid lobes were able to iodinate arachidonic acid and docosahexaenoic acids in vitro. Meanwhile 6-iodo-5 hydroxy-eicosa trienoic acid (delta-iodolactone) has been identified in human thyroid tissue, but only after treating the patients with high doses of iodin e before thyroidectomy, whereas in untreated endemic goiter this delta -iodolactone could not be found. In rats treated with iodolactones, me thimazole induced goiter formation could be prevented. In human and po rcine thyroid cells in vitro, delta-iodolactone inhibited epidermal gr owth factor (EGF) induced proliferation in 50-fold lower concentration s than iodide itself. Furthermore it could be demonstrated that only t he IP3-, but not the cAMP generation in porcine thyroid cells could be inhibited by this compound. Also a structure specifity for delta-iodo lactones for the biological activity could be shown. We will summarize and discuss these important new findings on the role of iodolactones on thyroid growth.