Retinoic acid modulation of thyroid dual oxidase activity in rats and its impact on thyroid iodine organification.
The sodium-iodide symporter (NIS) mediates iodide uptake into the thyrocytes, which is important for the diagnosis and therapy of thyroid disorders. Decreased ability to uptake iodide in thyroid carcinomas reduces the efficacy of radioiodine therapy, and retinoic acid (RA) treatment reinduces iodide uptake. The effectiveness of treatment depends not only on iodide uptake but also on the ability of thyrocytes to organify iodine, which is catalyzed by thyroperoxidase (TPO) in the presence of H(2)O(2). Our goal was to determine the influence of RA on thyroid iodide uptake, iodine organification, and TPO and dual oxidase (DuOx) activities. Normal rats were treated with all-trans-RA or 13-cis-RA (100 or 1500 microg/100 g body weight (b.w.), s.c.) for 14 and 28 days. The 2 h thyroid radioiodine content significantly decreased in rats treated with all-trans-RA (100 microg/100 g b.w.) for 14 days. In this group, NIS function and TPO activity were unchanged, whereas DuOx activity was significantly decreased, which might have contributed to the decrease in iodine organification. Both doses of 13-cis-RA for 28 days increased the 15 min thyroid radioiodine uptake, while the 2 h radioiodide uptake increased only in rats treated with the highest dose of 13-cis-RA. While TPO activity did not change, H(2)O(2) generation was increased in this group, and serum thyroxine levels were normal. Since radioiodine half-life in the thyroid gland is important for treatment efficacy, our results highlight the importance of correctly choosing the RA isomer, the time and the dose of treatment, in order to improve the efficacy of radioiodine therapy.
Mühlbauer
Mônica
M
Laboratório de Fisiologia Endócrina, Instituto de Biofísica Carlos Chagas Filho, CCS - Bloco G - Cidade Universitária, Ilha do Fundão, Rio de Janeiro 21949-900, Brazil.
da Silva
Alba Cenélia Matos
AC
Marassi
Michelle Porto
MP
Lourenço
Alexandre Lopes
AL
Ferreira
Andrea Claudia Freitas
AC
de Carvalho
Denise Pires
DP
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000074623:Dual Oxidases; D007454:Iodides / Q000378:metabolism; D007455:Iodine / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D019255:NADPH Oxidases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D000099209:Sodium-Iodide Symporters
D000074623:Dual Oxidases; D007454:Iodides; D007455:Iodine; D019255:NADPH Oxidases; D027981:Symporters; D013974:Thyroxine; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters; C524752:Duox1 protein, rat