CHROMOGRANINS IN NEUROENDOCRINE TUMOR CELLS

嗜铬粒蛋白是免疫学上不同的， 分泌蛋白质，仅在内分泌和 神经元细胞，在储存时集中其分泌产物 颗粒并在刺激时释放。 已知的是 嗜铬粒蛋白由内分泌肿瘤以高速率分泌， 但是调节嗜铬粒蛋白分泌的因子， 在正常情况下是未知的。 此外，没有任何函数 但一直被认为是嗜铬粒蛋白。 长期目标是 研究者需要了解 嗜铬粒蛋白 嗜铬粒蛋白可能在聚集中起重要作用， 将肽激素包装成储存颗粒，但模型 直到最近才有系统地研究这一点。 GH4C1 垂体瘤细胞系构成了这样的模型系统， 转移到储存室中的催乳素的量可以 严格监管。 此外，催乳素的诱导 储存与嗜铬粒蛋白C储存的诱导有关。 这是第一次证明任何嗜铬粒蛋白 在细胞培养系统中受激素调节， 嗜铬粒蛋白C在细胞内的某些方面起作用， 催乳素转变成颗粒。 描述的实验 旨在进一步探讨 催乳素和嗜铬粒蛋白C之间的关系 这些研究将回答以下问题： (1)激素是否调节GH4C1中嗜铬粒蛋白C的合成 细胞？ (2)嗜铬粒蛋白C是否以与催乳素相同的速率积累 在激素诱导下的GH4C1细胞中 (3)嗜铬粒蛋白C和催乳素是否存在于相同的细胞中， 在GH4C1细胞培养物中的相同颗粒中？ (4)嗜铬粒蛋白C的急性释放曲线是什么 GH4C1细胞的催乳素 (5)什么是物理化学之间的相互作用的性质 嗜铬粒蛋白C和催乳素 这些研究将是GH4C1细胞系的独特性质 不仅要获得影响因素的基本知识， 嗜铬粒蛋白的产生和细胞含量，而且 确定嗜铬粒蛋白在激素储存中的重要性， 这是一个典型的神经内分泌细胞系。

The chromogranins are a family of immunologically distinct, secretory proteins that are expressed only in endocrine and neuronal cells that concentrate their secretory product in storage granules and release it upon stimulation. It is known that chromogranins are secreted at high rates by endocrine neoplasms, but the factors which regulate the secretion of chromogranins even under normal conditions are unknown. Furthermore, no function has yet been ascribed to the chromogranins. The long-term goal of this investigator is to understand the biological role of the chromogranins. Chromogranins may play an integral role in the aggregation and packing of peptide hormones into storage granules, but model systems to study this have been lacking until recently. The GH4C1 pituitary tumor cell line constitutes such a model system as the amount of prolactin diverted into a storage compartment can be hormonally regulated. Furthermore, the induction of prolactin storage is associated with an induction of chromogranin C storage. This is the first demonstration that any of the chromogranins can be regulated by hormones in cell culture system and suggests that chromogranin C functions intracellularly in some aspect of the diversion of prolactin into granules. The experiments described in this proposal are designed to further explore the relationship between prolactin and chromogranin C storage. The following questions will be answered by these studies: (1) Do hormones regulate the synthesis of chromogranin C in GH4C1 cells? (2) Does chromogranin C accumulate at the same rate as prolactin in GH4C1 cells under hormonal induction? (3) Are chromogranin C and prolactin found in the same cells and in the same granules in GH4C1 cell cultures? (4) What are the profiles of the acute release of chromogranin C and prolactin from GH4C1 cells? (5) What is the nature of the physicochemical interaction between chromogranin c and prolactin? These studies will be the unique properties of the GH4C1 cell line not only to gain fundamental knowledge of the factors which affect the production and cellular content of chromogranins, but also to establish the importance of chromogranins in hormone storage in this representative neuroendocrine cell line.