GLYCOSYLATION OF GLYCOPROTEIN HORMONE FREE SUBUNIT DURING PREGNANCY: DEVELOPMENT

妊娠期间糖蛋白无激素亚基的糖基化：发育

• 批准号: 6123246
• 负责人: DIANA L BLITHE
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6123246
• 关键词: biological products; biomaterials; biomedical resource; carbohydrates; female; growth /development; hormones; human subject; human tissue; lymphatic system; mother /infant health care; reproductive system; structural biology

. The glycoprotein hormone a subunit is common to the heterodi-ineric hormones CG,LH, FSH, and TSH. However, in its free form, it is an important placental and pituitary product and has been shown to have functions that are independent of the dimeric hormones. Glycosylation of free cc differs fi7om glycosylation of the combined form. The combination of cc and0 for heterodimer formation takes place in the ER prior to processing of the immature glycans. In cc subunits that have not combined with a 0 subunit, enzymes from the post-translational glycosylation machinery have access to substrate sites that are normally protected by the0 subunit of the heterodimer. As a result, the free form of oc subunit generally contains more elaborate oligosaccharide branching, as well as higher amounts of core fucosylation than a subunit obtained from dissociated hormone. These characteristic glycosylation patterns prevent secreted free (x subunits from combining with 0 subunits that might be encountered extracellularly, thus ensuring a population of free (x molecules. The (x subunit is a major placental product and its glycosylation was found to change dramatically during the advancement of pregnancy. In this collaboration, we have analyzed the glycosylation changes in five normal pregnancies. ESI NIS studies have indicated higher core-fucosylation, as well as changes in branching of glycans. The glycans were also determined by high-pH anion-exchange chromatography and CID MS/N4S. Amounts of core-fucosylation and of triantennary glycans increased substantially from early to late second trimester, and a shift was observed from 1-4/1-3 toward predom~inantly 1-6/1-6-branched triantennary structures. The glycosylation changes occurred in all individuals examined at the same gestational period, suggesting developmental regulation of N-acetylglucosaminyl-transferases IV and V, and a 6-fucosyltransferase during normal pregnancy. These enzymatic activities also appear to be affected in malignant transformation of the trophoblast. The findings have important implications for the proposed use of specific forms of glycosylation as markers for cancer, as the relative amounts of these glycans in normal pregnancy will be determined by gestational age.

。 糖蛋白激素的一个亚基是常见的 异二烯激素 CG、LH、FSH 和 TSH。 然而，在其免费 它是一种重要的胎盘和垂体产物，已被 显示具有独立于二聚体激素的功能。 游离CC的糖基化不同于组合CC的糖基化 形式。 cc 和 0 的组合用于形成异二聚体需要 在加工未成熟聚糖之前将其放入内质网中。 抄送 未与 0 亚基结合的亚基，来自 翻译后糖基化机器可以接触底物 通常受异二聚体的 0 亚基保护的位点。 因此，游离形式的 oc 亚基通常含有更多 复杂的寡糖分支，以及更多的核心 岩藻糖基化比从解离激素获得的亚基更重要。 这些 特征性糖基化模式可防止分泌游离（x 与可能遇到的 0 个子单元结合的子单元 细胞外，从而确保自由 (x 分子) 的群体。 （x 亚基是主要的胎盘产物，其糖基化是 发现在怀孕期间发生了巨大的变化。 在 在这次合作中，我们分析了五个方面的糖基化变化 正常怀孕。 ESI NIS 研究表明更高 核心岩藻糖基化，以及聚糖分支的变化。 这 还通过高 pH 阴离子交换色谱法测定聚糖 和 CID MS/N4S。 核心岩藻糖基化和三触角的量 聚糖从妊娠中期早期到中期显着增加， 并且观察到从 1-4/1-3 向占主导地位的转变 1-6/1-6-支化三触角结构。 糖基化发生变化 发生在同一妊娠期接受检查的所有个体中， 提示发育调节 N-乙酰氨基葡萄糖转移酶 IV 和 V，以及 6-岩藻糖基转移酶 正常怀孕期间。 这些酶的活性似乎也 影响滋养细胞的恶性转化。 研究结果 对拟议使用特定形式的 糖基化作为癌症的标志物，因为这些糖基化的相对量 正常妊娠中的聚糖将由胎龄决定。