The inhibition of PB125I formation in calf thyroid caused by 14-iodo-15-hydroxy-eicosatrienoic acid is due to decreased H2O2 availability.
Previous work from our laboratory has shown that 14-iodo-15-hydroxy-5,8,11-eicosatrienoic acid (I-HO-A) is a potent inhibitor of iodine organification in calf thyroid slices. The present studies were performed in order to clarify the mechanism of this action. Incubation of thyroid slices with 10(-4)M I-HO-A caused a 47 and 53% decrease in PB125I formation after 30 and 60 min incubation, respectively. In a series of experiments an inverse relationship between the degree of inhibition caused by I-HO-A and total iodine content and basal iodoprotein formation was observed. Chromatographic analysis of the labeled compounds showed a significant decrease in 125I incorporation into MIT, DIT, T3 and total iodolipid. The site of the inhibitory effect of I-HO-A was then sought. TPO was measured by three different methods. When TPO was solubilized from I-HO-A treated slices, no change in enzymatic activity was observed. Moreover, the same lack of action was found when solubilized TPO was incubated with I-HO-A. The production and release of H2O2 into the incubation medium was measured by chemiluminiscence technique. In control slices the values increased during the first 10 min and reached a plateau. Pretreatment of the slices with 10(-4)M KI caused a 51% inhibition, while the same concentration of I-HO-A produced a 59% inhibition. The possibility that I-HO-A might exert its action through a putative protein inhibitor was also explored. Incubation of slices with 10(-5)M I-HO-A caused a 46% decrease in PB125I formation and addition of actinomycin D or puromycin failed to alter this effect.(ABSTRACT TRUNCATED AT 250 WORDS)
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002417:Cattle; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000096:biosynthesis / Q000172:deficiency*; D007455:Iodine / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D007467:Iodoproteins / Q000037:antagonists & inhibitors*; D011877:Radionuclide Imaging; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000378:metabolism*
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D007457:Iodine Radioisotopes; D007467:Iodoproteins; C055893:14-iodo-15-hydroxy-5,8,11-eicosatrienoic acid; D016718:Arachidonic Acid; D007455:Iodine; D006861:Hydrogen Peroxide; D015126:8,11,14-Eicosatrienoic Acid