Tissue-specific Posttranslational Modification Allows Functional Targeting of Thyrotropin

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2014 Dec 2

PMID 25437536

Citations 39

Authors

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

Soon will be listed here.

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.

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