Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes

Kenzaburo Oda; Yuqian Luo; Aya Yoshihara; Yuko Ishido; Kengo Sekihata; Kensei Usukura; Mariko Sue; Naoki Hiroi; Takahisa Hirose; Koichi Suzuki

doi:10.1016/j.bbrc.2016.12.109

Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes

Biochem Biophys Res Commun. 2017 Jan 29;483(1):541-546. doi: 10.1016/j.bbrc.2016.12.109. Epub 2016 Dec 18.

Authors

Kenzaburo Oda¹, Yuqian Luo², Aya Yoshihara³, Yuko Ishido⁴, Kengo Sekihata⁵, Kensei Usukura⁶, Mariko Sue⁷, Naoki Hiroi⁸, Takahisa Hirose⁹, Koichi Suzuki¹⁰

Affiliations

¹ Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002, Japan; Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540, Japan. Electronic address: kenzaburou.oda@med.toho-u.ac.jp.
² Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002, Japan. Electronic address: yuqianluo31@gmail.com.
³ Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002, Japan; Department of Education Planning and Development, Faculty of Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540, Japan. Electronic address: aya.yoshihara@med.toho-u.ac.jp.
⁴ Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002, Japan. Electronic address: yishidora@gmail.com.
⁵ Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan. Electronic address: hdskbb7@gmail.com.
⁶ Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan. Electronic address: kensei533@gmail.com.
⁷ Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002, Japan; Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540, Japan. Electronic address: msue@med.toho-u.ac.jp.
⁸ Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540, Japan; Department of Education Planning and Development, Faculty of Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540, Japan. Electronic address: n-hiroi@med.toho-u.ac.jp.
⁹ Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540, Japan. Electronic address: takahisa.hirose@med.toho-u.ac.jp.
¹⁰ Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002, Japan. Electronic address: koichis0923@med.teikyo-u.ac.jp.

PMID: 27998776
DOI: 10.1016/j.bbrc.2016.12.109

Abstract

Thyroglobulin (Tg) stored in thyroid follicles exerts a potent negative-feedback effect on each step of pre-hormone biosynthesis, including Tg gene transcription and iodine uptake and organification, by suppressing the expression of specific transcription factors that regulate these steps. Pre-hormones are stored in the follicular colloid before being reabsorbed. Following lysosomal proteolysis of its precursor, thyroid hormone (TH) is released from thyroid follicles. Although the suppressive effects of follicular Tg on each step of pre-hormone biosynthesis have been extensively characterized, whether follicular Tg accumulation also affects hormone reabsorption, proteolysis, and secretion is unclear. In this study we explored whether follicular Tg can regulate the expression and function of the lysosomal endopeptidases cathepsins. We found that in the rat thyroid cell line FRTL-5 follicular Tg induced cathepsin H mRNA and protein expression, as well as cathepsin H enzyme activity. Double immunofluorescence staining showed that Tg endocytosis promoted cathepsin H translocalization into lysosomes where it co-localized with internalized Tg. These results suggest that cathepsin H is an active participant in lysosome-mediated pre-hormone degradation, and that follicular Tg stimulates mobilization of pre-hormones by activating cathepsin H-associated proteolysis pathways.

Keywords: Cathepsin H; Thyroglobulin; Thyroid hormone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cathepsin H / metabolism*
Cell Line
Dose-Response Relationship, Drug
Endocytosis
Gene Expression Regulation
Lysosomes / metabolism
Microscopy, Fluorescence
RNA, Messenger / metabolism
Rats
Real-Time Polymerase Chain Reaction
Thyroglobulin / metabolism*
Thyroid Epithelial Cells / metabolism*
Thyroid Gland / metabolism*

Substances

RNA, Messenger
Thyroglobulin
Cathepsin H