Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors.
Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors.
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蓖麻毒素和扁豆凝集素亲和层析揭示了 12 种人类垂体瘤分泌的促甲状腺素的寡糖异质性。
DOI：
10.1016/0026-0495(92)90129-x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Rubin,D
中科院分区：
文献类型：
--
作者：
Magner,J;Klibanski,A;Fein,H;Smallridge,R;Blackard,W;YoungJr,W;Ferriss,JB;Murphy,D;Kane,J;Rubin,D
尽管血清中TSH水平相似，但一些促甲状腺激素（TSH）分泌型垂体瘤患者的甲状腺功能亢进程度高于其他患者，这表明不同肿瘤可能分泌具有不同生物活性的不同TSH分子。我们使用蓖麻毒素和小扁豆凝集素亲和层析，以测试是否TSH寡糖12例TSH产生的肿瘤之间的变化。我们发现，每个肿瘤分泌的TSH异构体，其暴露的半乳糖（Gal）残基的程度不同，唾液酸化和核心岩藻糖基化的程度。这些生化参数也有显着差异的TSH分泌不同的肿瘤。异构体似乎反映了两个肿瘤中唾液酸转移酶活性差，其余肿瘤中唾液酸转移酶活性高。肿瘤分泌的TSH比对照甲状腺功能正常者分泌的TSH更岩藻糖基化。肿瘤TSH的唾液酸化和岩藻糖基化之间呈负相关。TSH寡糖结构和生物活性之间没有明显的简单关系，尽管具有最少和最多唾液酸化TSH的同种型的混合物在临床上似乎是最具生物活性的。在血清和培养基TSH均可用的三名患者中，血清中的TSH比肿瘤体外分泌的TSH更唾液酸化，这可能反映了唾液酸化亚型从循环中的缓慢清除。血清TSH的核心岩藻糖基化程度低于培养基TSH。这些数据证明人类肿瘤分泌具有异质寡糖结构的TSH。
Some patients with thyrotropin (TSH)-producing pituitary tumors are more hyperthyroid than others despite similar TSH levels in serum, suggesting that qualitatively different TSH molecules with differing bioactivities may be secreted by different tumors. We used ricin and lentil lectin-affinity chromatography to test whether the TSH oligosaccharides varied among 12 patients with TSH-producing tumors. We found that each tumor secreted heterogeneous isoforms of TSH that differed in their extents of exposed galactose (Gal) residues, and their degrees of sialylation and core fucosylation. These biochemical parameters also varied markedly for TSH secreted by different tumors. Isoforms appeared to reflect poor sialyltransferase activity in two tumors and efficient sialyltransferase in the remainder. TSH secreted by tumors was more fucosylated than TSH secreted by control euthyroid persons. There was an inverse relationship between the sialylation and fucosylation of tumor TSH. No simple relationship between TSH oligosaccharide structures and bioactivity was evident, although mixtures of isoforms having the least and most sialylated TSH seemed to be the most bioactive clinically. In three patients from whom serum and medium TSH were both available, TSH in serum was more sialylated than TSH secreted by the tumor in vitro, perhaps reflecting slow clearance of sialylated isoforms form the circulation. Core fucosylation of serum TSH was less than that of medium TSH. These data prove that human tumors secrete TSH with heterogeneous oligosaccharide structures.