title: Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes.
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.
authors.affiliation: 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.
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Oda
authors.affiliation: 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.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshihara
authors.affiliation: 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.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishido
authors.affiliation: 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.
authors.forename: Kengo
authors.initials: K
authors.lastname: Sekihata
authors.affiliation: 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.
authors.forename: Kensei
authors.initials: K
authors.lastname: Usukura
authors.affiliation: 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.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sue
authors.affiliation: 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.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiroi
authors.affiliation: 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.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
authors.affiliation: 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.
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D056655:Cathepsin H / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D005786:Gene Expression Regulation; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013954:Thyroglobulin / Q000378:metabolism*; D000072637:Thyroid Epithelial Cells / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D013954:Thyroglobulin; D056655:Cathepsin H
keywords: Cathepsin H; Thyroglobulin; Thyroid hormone