The TSH receptor (TSHR) on the surface of thyrocytes is unique among the glycoprotein hormone receptors in comprising two subunits: an extracellular A-subunit, and a largely transmembrane and cytosolic B-subunit. Unlike its ligand TSH, whose subunits are encoded by two genes, the TSHR is expressed as a single polypeptide that subsequently undergoes intramolecular cleavage into disulfide-linked subunits. Cleavage is associated with removal of a C-peptide region, a mechanism similar in some respects to insulin cleavage into disulfide linked A- and B-subunits with lossofaC-peptideregion. The potential pathophysiological importance of TSHR cleavage into A-and B-subunits is that some A-subunits are shed from the cell surface. Considerable experimental evidence supports the concept that A-subunit shedding in genetically susceptible individuals is a factor contributing to the induction and/or affinity maturation of pathogenic thyroid-stimulating autoantibodies, the direct cause of Graves' disease. The noncleaving gonadotropin receptors are not associated with autoantibodies that induce a "Graves' disease of the gonads." We also review herein current information on the location of the cleavage sites, the enzyme(s) responsible for cleavage, the mechanism by which A-subunits are shed, and the effects of cleavage on receptor signaling. (Endocrine Reviews 37: 114-134, 2016).

中文翻译：

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TSH受体切割成亚基并脱落A亚基; 分子和临床观点。

甲状腺细胞表面的TSH受体（TSHR）在糖蛋白激素受体中是独特的，它包含两个亚基：细胞外A亚基和大部分跨膜和胞质B亚基。与其配体TSH（其亚基由两个基因编码）不同，TSHR被表达为单个多肽，随后将其分子内切割成二硫键连接的亚基。切割与C肽区域的去除有关，该机制在某些方面类似于胰岛素切割为具有丢失C肽区域的二硫键连接的A和B亚基。TSHR裂解为A和B亚基的潜在病理生理重要性是某些A亚基从细胞表面脱落。大量实验证据支持这样的概念，即遗传易感个体中的A亚基脱落是导致致病性甲状腺刺激性自身抗体（Graves病的直接原因）的诱导和/或亲和力成熟的因素。未裂解的促性腺激素受体与诱导“性腺的格雷夫斯病”的自身抗体无关。我们还在本文中综述了有关切割位点的位置，负责切割的酶，A-亚基脱落的机理以及切割对受体信号传导的影响的当前信息。（内分泌评论37：114-134，2016）。未裂解的促性腺激素受体与诱导“性腺的格雷夫斯病”的自身抗体无关。我们还在本文中综述了有关切割位点的位置，负责切割的酶，A-亚基脱落的机理以及切割对受体信号传导的影响的当前信息。（内分泌评论37：114-134，2016）。未裂解的促性腺激素受体与诱导“性腺的格雷夫斯病”的自身抗体无关。我们还在本文中综述了有关切割位点的位置，负责切割的酶，A-亚基脱落的机理以及切割对受体信号传导的影响的当前信息。（内分泌评论37：114-134，2016）。