NORMAL AND NEOPLASTIC HUMAN PITUITARY TISSUE

描述：脑垂体瘤与许多 因荷尔蒙分泌过多和/或空间引起的发病率 占位性病变。垂体瘤生长调控机制的研究进展 人们对人类知之甚少。这项提案将审查这项规定 正常人和肿瘤患者激素分泌与细胞生长的关系 应用形态学、免疫组织化学、 生化和杂交方法。嗜铬颗粒蛋白的作用 (Cg)/分泌性颗粒素(Sg)及其对激素的蛋白分解产物 分泌物和对细胞生长的影响将被研究。初步研究 已经证明，来自CGA的x：U是由脑下垂体分泌的。 培养中的细胞对下丘脑多肽的反应 嗜铬抑素和ATE对培养的垂体腺激素分泌的调节 肿瘤。原转化酶PC2和PC3在植物生长发育过程中的作用 Cg/Sg将在脑垂体瘤中进行分析。可能的 催乳素(PRL)及其受体(PRL-R)的自分泌/旁分泌作用 垂体瘤的生长和激素分泌将是 碱性成纤维细胞生长因子的研究及作用 并将检测其在脑垂体细胞中的受体和肿瘤功能 利用免疫组织化学技术和反向溶血空斑 测定脑垂体细胞释放碱性成纤维细胞生长因子的方法 缺乏特定的下丘脑多肽。初步研究表明 研究表明，下丘脑多肽可以增加脑垂体中bFGFmRNA的表达 细胞。劳埃德博士将建立脑下垂体瘤细胞系 SV40重组体感染垂体细胞并诱导细胞分化 为了获得增殖能力较强的细胞系进行大系列的 为同样的肿瘤做实验。这项研究的长期目标 是为了分析荷尔蒙和生长因子 影响垂体细胞生长和激素分泌，这可能导致 为了更好地了解脑垂体瘤的发展和 更有效的治疗方式。

DESCRIPTION: Pituitary neoplasms are associated with a great deal of morbidity because of excessive hormone production and/or as space occupying lesions. The mechanisms regulating pituitary tumor growth in humans are poorly understood. This proposal will examine the regulation of hormone production and cell growth in normal and neoplastic human pituitary gland tissues using morphological, immunohistochemical, biochemical and hybridization methods. The role of chromogranins (Cg)/secretogranins (Sg) and their proteolytic products on hormone secretion and on cell growth will be investigated. Preliminary studies have shown that x:u, which is derived from CgA, is secreted by pituitary cells in culture in response to hypothalamic peptides and that chromostatin and ate regulate hormone secretion in cultured pituitary tumors. The role of the proconvertases PC2 and PC3 in the processing of Cg/Sg will be analyzed in pituitary tumors. The possible autocrine/paracrine role of prolactin (PRL) and its receptor (PRL-R) in the growth and hormone secretion in pituitary tumors will be investigated and the effects of basic fibroblast growth factor (bFGF) and its receptors in pituitary cell and tumor function will be examined using immunohistochemical techniques and the reverse hemolytic plaque assay to assess release of bFGF by pituitary cells in the presence or absence of specific hypothalamic peptides. Preliminary studies have shown that hypothalamic peptides can increase bFGF mRNA in pituitary cells. Dr. Lloyd will establish cell lines from pituitary tumors using SV40 recombinants to infect pituitary cells and induce cell proliferation in order to obtain cell lines to perform large series of experiments for the same tumors. The long term objectives o this study are to analyze the mechanisms by which hormones and growth factors influence growth and hormone secretion in pituitary cells which may lead to a better understanding about the development of pituitary tumors and to more effective treatment modalities.