Ikegami Keisuke, Liao Xiao-Hui, Hoshino Yuta, Ono Hiroko, Ota Wataru, Ito Yuka, Nishiwaki-Ohkawa Taeko, Sato Chihiro, Kitajima Ken, Iigo Masayuki, Shigeyoshi Yasufumi, Yamada Masanobu, Murata Yoshiharu, Refetoff Samuel, Yoshimura Takashi
Laboratory of Animal Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Cell Rep. 2014 Nov 6;9(3):801-10. doi: 10.1016/j.celrep.2014.10.006. Epub 2014 Oct 30.
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.
促甲状腺激素（TSH；促甲状腺素）是一种由垂体分泌的糖蛋白。远侧部来源的TSH（PD-TSH）刺激甲状腺产生甲状腺激素（THs），而结节部来源的TSH（PT-TSH）作用于下丘脑以调节季节性生理和行为。然而，尚不清楚这两种TSH如何避免功能上的相互干扰。在此，我们表明这种调节是由组织特异性糖基化介导的。尽管PT-TSH释放到循环中，但它不会刺激甲状腺。已知PD-TSH具有硫酸化的双天线N-聚糖，并且硫酸化的TSH在肝脏中会迅速代谢。相比之下，PT-TSH具有唾液酸化的多分支N-聚糖；在循环中，它与免疫球蛋白或白蛋白形成大TSH复合物，导致其生物活性丧失。糖基化对于广泛的生物学过程至关重要。本报告证明了其参与防止体内信号分子的功能相互干扰。
