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Cell Rep. 2014 Nov 6;9(3):801-10. doi: 10.1016/j.celrep.2014.10.006. Epub 2014 Oct 30.

Tissue-specific posttranslational modification allows functional targeting of thyrotropin.

Author information

1
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
2
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
3
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.
4
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.
5
Department of Applied Biological Chemistry, Faculty of Agriculture, C-Bio, and CORE, Utsunomiya University, 350 Mine-machi, Utsunomiya 321-8505, Japan.
6
Department of Anatomy and Neurobiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
7
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
8
Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
9
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.
10
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.

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.

PMID:
25437536
PMCID:
PMC4251493
DOI:
10.1016/j.celrep.2014.10.006
[Indexed for MEDLINE]
Free PMC Article

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