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The H2O2-Generating System Modulates Protein Iodination and the Activity of the Pentose Phosphate Pathway in Dog Thyroid^*

BERNARD CORVILAIN, JACQUELINE VAN SANDE, ERIC LAURENT and JACQUES E. DUMONT

Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels Campus Erasme, B-1070 Brussels, Belgium

Abstract

Iodide oxidation and binding to proteins require a thyroperoxidase and an ill defined H₂O₂-generating system. The NADP⁺ supply and, thus, NADPH oxidation are the limiting steps of the pentose phosphate pathway. The purpose of this work was to test the hypothesis that H₂O₂ generation is a limiting step of iodination and NADPH oxidation and, therefore, of the pentose phosphate pathway. H₂O₂ produced by dog thyroid slices was measured with the homovanillic fluorescence assay. Our data show that H₂O₂ generation is stimulated by both the cAMP cascade [as activated by TSH, forskolin and (Bu)₂cAMP] and the Ca²⁺-phosphatidylinositol cascade (as activated by carbamylcholine, ionomycin, and 12-O-tetradecanoylphorbol-13- acetate). We used several physiological and pharmacological agents that modulate iodide organification. In all cases there was a strict parallelism between effects on H₂O₂ generation, iodide binding to proteins, and pentose phosphate pathway activity. Moreover, in TSH- or carbamylcholine-stimulated slices, glucose or Ca²⁺ depletion, which greatly depressed H₂O₂ generation, also greatly decreased iodide organification and the activity of the pentose phosphate pathway. The glutathione peroxidase-catalyzed H₂O₂ reduction in the cytosol, which involves NADPH oxidation and, therefore, increases the NADP supply, also enhances the activity of the pentose phosphate pathway.

All of these data strongly support the hypothesis that H₂O₂ generation in dog thyroid controls iodination of proteins; through the NADPH oxidation resulting from H₂O₂ production and reduction, hydrogen peroxide also regulates the activity of the pentose phosphate pathway. (Endocrinology 128: 779–785, 1991)

Footnotes

^* This work was supported by grants from the Ministere de la Politique Scientifique, the Fonds de la Recherche Scientifique, and the Fonds de la Recherche Scientifique Medicale.

Fellow of the Erasmus Hospital Foundation (ULB, Brussels). Since October 1988, he has been a fellow of the Fonds National de la Recherche Scientifique (FNRS) Belgium.

Received June 19, 1990.

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