Inhibitory effects of methimazole and propylthiouracil on iodotyrosine deiodinase 1 in thyrocytes

Aya Yoshihara; Yuqian Luo; Yuko Ishido; Kensei Usukura; Kenzaburo Oda; Mariko Sue; Akira Kawashima; Naoki Hiroi; Koichi Suzuki

doi:10.1507/endocrj.EJ18-0380

ORIGINAL

Inhibitory effects of methimazole and propylthiouracil on iodotyrosine deiodinase 1 in thyrocytes

Aya Yoshihara, Yuqian Luo, Yuko Ishido, Kensei Usukura, Kenzaburo Oda, Mariko Sue, Akira Kawashima, Naoki Hiroi, Koichi Suzuki

Author information

Aya Yoshihara
Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan
Center for Medical Education, Faculty of Medicine, Toho University, Ota, Tokyo 143-8540, Japan
Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Sumida, Tokyo 130-8575, Japan
Yuqian Luo
Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan
Yuko Ishido
Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan
Kensei Usukura
Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan
Kenzaburo Oda
Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan
Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Sumida, Tokyo 130-8575, Japan
Mariko Sue
Department of Medicine III, Faculty of Medicine of the Technische Universität Dresden, Dresden 01307, Germany
Akira Kawashima
Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan
Naoki Hiroi
Center for Medical Education, Faculty of Medicine, Toho University, Ota, Tokyo 143-8540, Japan
Koichi Suzuki
Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo 173-8605, Japan

Keywords: Iodotyrosine deiodinase 1 (Dehal1), Methimazole (MMI), Propylthiouracil (PTU), Iodine, Thyroglobulin

JOURNAL FREE ACCESS FULL-TEXT HTML

2019 Volume 66 Issue 4 Pages 349-357

DOI https://doi.org/10.1507/endocrj.EJ18-0380

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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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