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Negative correlation between thyroperoxidase and dual oxidase H₂O₂-generating activities in thyroid nodular lesions

¹ Laboratório de Fisiologia Endócrina Doris Rosenthal from Instituto de Biofísica Carlos Chagas Filho and Serviços de² Endocrinologia and³ Cirurgia from Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21949-900, Brasil

(Correspondence should be addressed to D P de Carvalho who is now at Instituto de Biofísica Carlos Chagas Filho, CCS-Bloco G- Cidade Universitária, Ilha do Fundão, Rio de Janeiro, 21949-900, Brasil; Email: dencarv{at}biof.ufrj.br)

Iodine incorporation into thyroglobulin is dependent on the activities of both thyroperoxidase (TPO) and thyroid dual oxidase 2 (DuOx2). Although TPO expression is decreased in some thyroid nodular lesions, DuOx1 and 2 mRNA expressions are maintained, but DuOx H₂O₂-generating activity has never been evaluated in such tumors. Our goal was to determine DuOx activity in hypofunctioning lesions of the thyroid. We evaluated H₂O₂ generation by DuOx in 12 paranodular to cold nodule samples, 17 non-toxic multinodular goiters (MNG; 33 samples), 3 papillary carcinomas (PC; 4 samples), 3 follicular carcinomas (FC; 4 samples), and 10 follicular adenomas. DuOx activity was detected in all paranodular tissues (121±23 nmol H₂O₂/h per mg protein), but was undetectable (<1 nmol H₂O₂ generated) in all PC, two out of four FC samples and seven out of ten adenomas. In 11 MNG at least two different areas of the goiter have been evaluated, and in 5 of these goiters one of the samples had DuOx activity below the limit of detection. The coefficient of variation in MNG samples ranged from 11.3 to 57.2%. Interestingly, in all the adenomas studied, TPO activity (486±142 U/g protein, n=8) was well within the range found in paranodular tissues (414±116 U/g protein, n=3). We found a significant negative correlation between DuOx and TPO activities, suggesting that these enzymes are regulated in opposite directions, at least in thyroid tumors.