MICROHETEROGENEITY OF HUMAN ALPHA-FETOPROTEIN

甲胎蛋白(AFP)是一种高表达的糖蛋白。 在怀孕期间的数量。AFP在生物化学上显示电荷凝集素 微观异质性。我们实验室的结果表明， 甲胎蛋白的微异质性在正常状态下发生显著变化 发展。然而，目前还不能确定这些发现是否 反映AFP功能的生理变化或仅仅表明 这种糖蛋白的生物化学变化。 从足月核心血中分离出的甲胎蛋白，虽然本身不是有丝分裂原，但可以 增强生长因子的有丝分裂活性，并可能起到 在胎儿发育过程中调节细胞增殖。没有丝裂原 在妊娠中期的羊水中观察到活性，这也是 含有升高的甲胎蛋白水平。因此，AFP的增殖活性可能 随胎儿发育而变化。发展与发展之间的关系 甲胎蛋白微观异质性和生物活性的变化是主要的 利息。 在这里提出的一系列实验中，我们将尝试 描述甲胎蛋白微异质性的发育特征和 生物活性。我们将以猴子为模型，小心地 定义这些个体发生的变化并补充和扩展数据 从使用人类胎儿的材料中获得，这显然是 有限的。AFP的电荷和凝集素的微观不均一性将是 在整个怀孕期间在物种中进行评估。猴子的胎儿组织会 在怀孕的不同阶段被移除，以允许表征 这些组织产生甲胎蛋白的能力。此外，我们将使用 无论是猴子还是人，都要阐明它们之间的关系 电荷和凝集素的微观异质性与甲胎蛋白的表达 增殖活性。最后，甲胎蛋白的生化基础 微生物的异质性和生物活性将被阐明。这个 这些研究的结果将极大地增加我们对 甲胎蛋白对正常胎儿的生化和生理意义 发展。

Alpha fetoprotein (AFP) is a glycoprotein which is produced in high amounts during pregnancy. Biochemically, AFP exhibits charge lectin microheterogeneity. Results from our laboratory have shown that the microheterogeneous nature of AFP changes markedly during normal development. However, it is currently not certain if these findings reflect a physiological change in AFP function or merely indicate an alteration in the biochemistry of this glycoprotein. AFP isolated from term core blood, although not mitogenic itself, can enhance the mitogenic activity of growth factors and may function to modulate cell proliferation during fetal development. No mitogenic activity was observed in midgestation amniotic fluid, which also contains increased levels of AFP. Thus, AFP proliferative activity may vary with fetal development. The relationship between developmental changes in AFP microheterogeneity and biological activity is of major interest. In the series of experiments proposed herein, we will attempt to characterize the developmental aspects of AFP microheterogeneity and biological activity. We will use the monkey as a model to carefully define these ontogenic changes and to compliment and extend data obtained from the use of human fetal material, which is obviously limited. The charge and lectin microheterogeneity of AFP will be evaluated in the species throughout gestation. Monkey fetal tissue will be removed at various stages of gestation to allow the characterization of the production of AFP by these tissues. Additionally, we will use both the monkey and the human to elucidate the relationships between charge and lectin microheterogeneity and the expression of AFP proliferative activity. Finally, the biochemical basis for AFP microheterogeneity and biological activity will be elucidated. The results of these studies will greatly add to our knowledge of the biochemical and physiological importance of AFP to normal fetal development.