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

Abstract

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 KI 0.1 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.(ABSTRACT TRUNCATED AT 250 WORDS)

The Protein Kinase C Pathway Inhibits Iodide Uptake by Calf Thyroid Cells via Sodium Potassium-Adenosine Triphosphatase

“…As previously shown by us (26), TSH stimulated ATPase activity, and the present studies showed that PMA reversed this effect. Moreover, PMA caused a similar degree of inhibition of both iodide uptake and Na 1 /K 1 ATPase, suggesting a causal link between these parameters.…”

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

“…A location of iodolactones at the cell membrane level may be suggested from the site of arachidonic acid release as well as from the inhibition by organic forms of iodine at or near the adenylate cyclase complex and the inhibition of inositol phosphate generation (Filetti and Rapoport 1983;Laurent, Mockel, Takazawa, Erneux and Dumont 1989). Indeed, IL-w was found to act at the cell membrane level (Krawiec, Chester, Bocanera, Pregliasco, Juvenal and Pisarev 1991).…”

Iodide Effects on the Thyroid

“…Pisarev and coworkers tested the effects of -iodolactone (6-iodo-5-hydroxyeicosatrienoic acid, -lactone), an -iodolactone (14-iodo-15-hydroxyeicosatrienoic acid, -lactone) and the free acid formed upon hydrolysis of -lactone (14-iodo-15-hydroxyeicosatrienoic acid). While iodide exerted its action at the membrane and transcriptional levels (inhibiting the expression of some thyroid-specific genes), the action of -iodolactone was mainly at the membrane level (Krawiec et al, 1991). In calf thyroid slices, the three compounds inhibited the incorporation of radioiodine into thyroid iodoproteins, as a result of decreased H 2 O 2 availability Krawiec et al, 1988).…”