title: Tissue-specific posttranslational modification allows functional targeting of thyrotropin.
abstract: Thyroid-stimulating hormone (TSH; thyrotropin) is a glycoprotein secreted from the pituitary gland. Pars distalis-derived TSH (PD-TSH) stimulates the thyroid gland to produce thyroid hormones (THs), whereas pars tuberalis-derived TSH (PT-TSH) acts on the hypothalamus to regulate seasonal physiology and behavior. However, it had not been clear how these two TSHs avoid functional crosstalk. Here, we show that this regulation is mediated by tissue-specific glycosylation. Although PT-TSH is released into the circulation, it does not stimulate the thyroid gland. PD-TSH is known to have sulfated biantennary N-glycans, and sulfated TSH is rapidly metabolized in the liver. In contrast, PT-TSH has sialylated multibranched N-glycans; in the circulation, it forms the macro-TSH complex with immunoglobulin or albumin, resulting in the loss of its bioactivity. Glycosylation is fundamental to a wide range of biological processes. This report demonstrates its involvement in preventing functional crosstalk of signaling molecules in the body.
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ikegami
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Liao
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ono
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ota
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Nishiwaki-Ohkawa
authors.affiliation: Laboratory of Animal Cell Function, Bioscience and Biotechnology Center and Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sato
authors.affiliation: Laboratory of Animal Cell Function, Bioscience and Biotechnology Center and Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kitajima
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, C-Bio, and CORE, Utsunomiya University, 350 Mine-machi, Utsunomiya 321-8505, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iigo
authors.affiliation: Department of Anatomy and Neurobiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Shigeyoshi
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA; Department of Pediatrics and Committee on Genetics, The University of Chicago, Chicago, IL 60637, USA. Electronic address: refetoff@uchicago.edu.
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Avian Bioscience Research Center, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Division of Seasonal Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki 444-8585, Japan. Electronic address: takashiy@agr.nagoya-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshimura
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D006031:Glycosylation; D007074:Immunoglobulin G / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
chemical_list: D000418:Albumins; D007074:Immunoglobulin G; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin