CHROMOGRANINS IN NEUROENDOCRINE TUMOR CELLS

嗜铬颗粒蛋白是一个免疫上截然不同的家族， 仅在内分泌和蛋白质中表达的分泌蛋白 集中其分泌产物储存的神经细胞 颗粒，并在刺激时释放。众所周知， 嗜铬颗粒素由内分泌肿瘤大量分泌， 但调节嗜铬粒细胞分泌的因素甚至 在正常情况下是未知的。此外，没有任何函数具有 但仍被归因于嗜铬颗粒。这样做的长期目标是 研究人员要了解细胞的生物学作用 嗜铬颗粒。 嗜铬颗粒可能在聚集和聚集中发挥不可或缺的作用 将多肽激素包装成储存颗粒，但模型 直到最近，一直缺乏研究这一问题的系统。GH4C1号 垂体瘤细胞系构成了这样一个模型系统 转移到储存室的催乳素的量可以是 荷尔蒙调节的。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一种嗜铬颗粒可以 在细胞培养系统中受到激素的调节，并提示 嗜铬颗粒蛋白C在细胞内的某些方面起作用 将催乳素转化为颗粒。所描述的实验 在本提案中都旨在进一步探讨两国关系 在催乳素和嗜铬粒蛋白C存储之间。 这些研究将回答以下问题： (1)激素对GH4C1中嗜铬粒蛋白C的合成有调节作用吗？ 细胞？ (2)嗜铬颗粒蛋白C的累积速度与催乳素相同吗？ 在激素诱导下的GH4C1细胞中？ (3)嗜铬粒蛋白C和催乳素是否在同一细胞中发现，以及 在GH4C1细胞培养中的相同颗粒中？ (4)嗜铬粒蛋白C急性释放的特征是什么 以及来自GH4C1细胞的催乳素？ (5)物理和化学相互作用的性质是什么 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 嗜铬颗粒素的生产和细胞含量，还可以 确定嗜铬颗粒素在激素储存中的重要性 这是一个具有代表性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.