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Inhibitory effects of methimazole and propylthiouracil on iodotyrosine deiodinase 1 in thyrocytes.
Yoshihara, Aya; Luo, Yuqian; Ishido, Yuko; Usukura, Kensei; Oda, Kenzaburo; Sue, Mariko; Kawashima, Akira; Hiroi, Naoki; Suzuki, Koichi.
Afiliação
  • Yoshihara A; Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan.
  • Luo Y; Center for Medical Education, Faculty of Medicine, Toho University, Ota, Tokyo 143-8540, Japan.
  • Ishido Y; Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Sumida, Tokyo 130-8575, Japan.
  • Usukura K; Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan.
  • Oda K; Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan.
  • Sue M; Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan.
  • Kawashima A; Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan.
  • Hiroi N; Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Sumida, Tokyo 130-8575, Japan.
  • Suzuki K; Department of Medicine III, Faculty of Medicine of the Technische Universität Dresden, Dresden 01307, Germany.
Endocr J ; 66(4): 349-357, 2019 Apr 25.
Article em En | MEDLINE | ID: mdl-30814441
ABSTRACT
Methimazole (MMI) and propylthiouracil (PTU) are commonly used for the treatment of Graves' disease. They share similar inhibitory effects on thyroid hormone biosynthesis by interfering with thyroid peroxidase (TPO)-mediated oxidation and organification of iodine. However, their potential effects on other thyroid functional molecules have not been explored in depth. To identify novel effects of MMI and PTU, DNA microarray analysis, real-time PCR, Western blotting, immunofluorescence staining and confocal laser scanning microscopy were performed using FRTL-5 rat thyroid cells. DNA microarray analysis indicated that both MMI and PTU suppress iodotyrosine deiodinase 1 (Iyd, Dehal1) mRNA levels. Further studies revealed that Dehal1 mRNA levels was stimulated by TSH, insulin and serum, while it was suppressed by iodine and a follicular concentration of thyroglobulin. MMI and PTU significantly suppressed Dehal1 expression induced by TSH, insulin and serum. On the other hand, although MMI suppressed Dehal1 expression in the absence of TSH, PTU only weakly suppressed Dehal1 without TSH. These results suggest that PTU and MMI may use different mechanisms to regulate Dehal1 expression, and TSH may play essential and differential roles in mediating PTU and MMI signals in thyrocytes. The drugs also inhibited re-distribution of Dehal1 protein into newly formed lysosomes following thyroglobulin endocytosis. These findings imply complex and multifaceted regulation of Dehal1 in the thyroid and suggest that MMI and PTU modulate Dehal1 expression and distribution of the protein in thyrocytes to exert their effect.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Propiltiouracila / Antitireóideos / Células Epiteliais da Tireoide / Iodeto Peroxidase / Metimazol Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Propiltiouracila / Antitireóideos / Células Epiteliais da Tireoide / Iodeto Peroxidase / Metimazol Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article