Tissue-Specific Posttranslational Modification Allows Functional Targeting of Thyrotropin
Keisuke Ikegami,
Xiao-Hui Liao,
Yuta Hoshino,
Hiroko Ono,
Wataru Ota,
Yuka Ito,
Taeko Nishiwaki-Ohkawa,
Chihiro Sato,
Ken Kitajima,
Masayuki Iigo,
Yasufumi Shigeyoshi,
Masanobu Yamada,
Yoshiharu Murata,
Samuel Refetoff,
Takashi Yoshimura
Affiliations
Keisuke Ikegami
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
Xiao-Hui Liao
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Yuta Hoshino
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
Hiroko Ono
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
Wataru Ota
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
Yuka Ito
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
Taeko Nishiwaki-Ohkawa
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
Chihiro Sato
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
Ken Kitajima
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
Masayuki Iigo
Department of Applied Biological Chemistry, Faculty of Agriculture, C-Bio, and CORE, Utsunomiya University, 350 Mine-machi, Utsunomiya 321-8505, Japan
Yasufumi Shigeyoshi
Department of Anatomy and Neurobiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
Masanobu Yamada
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
Yoshiharu Murata
Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
Samuel Refetoff
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Takashi Yoshimura
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
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.
