Abstract
Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompund. Data from different laboratories have shown that the thyroid is capable of producing different iodolipids, including iodinated derivatives of arachidonic acid; such as 5-hydroxy-6-iodo-8, 11, 14-eicosatrienoic-δ-lactone (IL-δ). Previous results from our laboratory showed that a semi-purified preparation of iodinated arachidonic acid exerts an inhibitory action in vitro on calf thyroid. In the present studies three purified iodinated derivatives of arachidonic acid were synthetized: IL-δ; 14-io-do-15-hydroxy-5, 8, 11-eicosatrienoic acid (I-OH-A) and its corresponding ω-lactone (IL-ω). Their action on MMI-induced goiter was studied in rats. Administration of MMI to rats during 10 days increased thyroid weight by 124%. This effect was significantly inhibited by the simultaneous injection of 5 μg/day of I-OH-A (57% inhibition of MMI action), IL-W (39%), IL-δ (33%) and T3 (95%), while arachidonic acid was without action. No inhibition was found with 1.25 μg/day KI, a dose equivalent to that which could be originated from total dehalogenation of the iodocompounds. These results support the idea that these iodocompounds have an intrinsic biologic activity and that there is a correlation between action and chemical structure. Serum TSH was increased around 15–20 fold after MMI administration. Chronic or acute injection of I-OH-A failed to alter TSH levels, indicating that this iodocompound exerts its action directly on the gland, without altering TSH concentration. Serum T3 and T4 were significantly decreased by MMI and addition of I-OH-A, did not change these values. Thyroidal cyclic AMP content was measured in the rats. Treatment with MMI increased cAMP, while injection of I-OH-A significantly decreased this action. These data suggest that this iodocompound acts at the step of cyclic AMP formation. Dose-response studies showed parallel decreases in gland weight, DNA and cAMP contents after I-OH-A treatment. The lowest effective dose was 3 μg/day. The present data demonstrate, for the first time, that some iodinated derivatives or arachidonic acid mimic the action of iodine on thyroid growth and cyclic AMP production and support the hypothesis that they may play a role in the autoregulatory mechanism.
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Supported in part by grants from the Argentine National Research Council (CO-NICET). Presented, in part at the 9th International Thyroid Congress, San Paulo, Brazil, September 1–5, 1985.
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Pisarev, M.A., Chazenbalk, G.D., Valsecchi, R.M. et al. Thyroid autoregulation. Inhibition of goiter growth and of cyclic AMP formation in rat thyroid by iodinated derivatives of arachidonic acid. J Endocrinol Invest 11, 669–674 (1988). https://doi.org/10.1007/BF03350212
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DOI: https://doi.org/10.1007/BF03350212