Thyroid Autoregulation: Evidence for an Action of Iodoarachidonates and Iodide at the Cell Membrane Level

 

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Summary

Iodolipids are the possible mediators of excess iodide in thyroid autoregulation. Previous work from our laboratory has shown that 14-iodo-15-hydroxy-5,8,11 eicosatrienoic acid (I-HO-A) and its omega lactone (IL-w) mimic the inhibitory action of excess iodide upon several parameters of thyroid metabolism.

The present experiments were performed in order to study the mechanism of the inhibitory effect of I-HO-A and IL-w on 2-deoxy-D-glucose (DOG) and aminoisobutyric acid (AIB) uptake by calf slices. I-HO-A, IL-w and KI0.1 mM caused a 33, 31 and 25% inhibition, respectively, of AIB uptake. The presence of 0.1 mM methimazole (MMI) only reversed the effect of KI. The transport of DOG was inhibited by both compounds: I-HO-A caused a 62% decrease, while IL-w produced a 64% inhibition; and MMI failed to relieve their action. On the contrary, the 33% inhibition caused by KI disappeared when MMI was present.

Taking into account that AIB and DOG transport across the membrane requires energy, supplied by Na-K-ATPase, changes in its activity were studied. TSH (10 mU/ml) produced a 74% increase in the enzyme activity which was significantly blocked by KI (82%), I-HO-A (100%) and IL-w (100%). Basal enzyme activity was impaired by IL-w (33%), but not by KI. These results were correlated with the decrease of DOG uptake produced by 1 mM ouabain.

Tissue specificity effect of iodoarachidonates was demonstrated by the absence of action on DOG transport in kidney and liver. IL-w showed a dose-response relationship for AIB and DOG uptake by calf thyroid slices. The present results demonstrate that the inhibition exerted by iodoarachidonates, on AIB and DOG uptake, in calf thyroid slices, is organ-specific, dose-dependent and may be produced, at least in part, by an impairment of Na-K-ATPase activity, which is involved in the energy contribution for this metabolic transport across the cell membrane.