REGULATION OF PITUITARY HYPERPLASIA AND NEOPLASIA

正常人群中控制增殖和分化的特异性因素 并对肿瘤大鼠垂体前叶细胞进行研究。角色 可能具有旁分泌功能的毛囊星状细胞 脑下垂体前叶将通过分离富集物进行检查 滤泡星状细胞群体的流式细胞术细胞分选 不连续Percoll密度梯度离心法。这些细胞 将通过免疫组织化学，电子显微镜，在 原位杂交和原位聚合酶链式反应及其在分子生物学中的应用 正常催乳素与生长发育富集群的培养研究 荷尔蒙细胞和肿瘤细胞系GH3。卵叶状星状 细胞在正常和增生性垂体中存在，但不存在。 在可移植的大鼠垂体细胞系中，所以这些分析应该 提供有关这些细胞在体内的调节作用的新信息 脑下垂体。转化生长因子β在血管紧张素转换酶中的作用 将研究垂体腺的生长和分化。我们的预赛 研究表明雌激素下调和基本成纤维细胞的生长 碱性成纤维细胞生长因子上调正常大鼠脑垂体中转化生长因子β1的表达 TGFbeta1可抑制GH3细胞系的细胞增殖。 生长速度快的GH3细胞株的体内外分析 在雌激素的刺激下，我们建立了一个垂体细胞系 实验室，其生长被雌激素抑制的GHRH-CL1将允许 美国将分析转化生长因子β对垂体细胞生长和分泌的影响 差异化。我们将使用一种由Target开发的细胞系 肿瘤发生，αT3-1，作为促性腺激素肿瘤的模型来了解更多 关于促性腺激素细胞的细胞增殖和分化 肿瘤。嗜铬粒蛋白/分泌颗粒蛋白及其α亚基 糖蛋白激素将作为肿瘤分化的标志物 一氧化氮合酶在该细胞系中的调控分析。《长河》 这项研究的短期目标是分析 激素和生长因子对细胞增殖和分化的影响 垂体组织，以了解更多关于正常和 肿瘤垂体腺细胞。这些研究的数据可能会导致 更好地了解垂体肿瘤的发展和可能 为治疗这些肿瘤提供更有效的手段。

Specific factors controlling proliferation and differentiation in normal and neoplastic rat anterior pituitary cells will be investigated. The role of folliculo-stellate cells which have putative paracrine functions in the anterior pituitary gland will be examined by isolating enriched populations of folliculo-stellate cells using flow cytometric cell sorting and discontinuous percoll density gradient centrifugation. These cells will be characterized by immunohistochemistry, electron microscopy, in situ hybridization and in situ polymerase chain reaction and used in co- culture studies with enriched populations of normal prolactin and growth hormone cells and with the neoplastic GH3 cell line. Folliculo-stellate cells are present in normal and hyperplastic pituitaries, but are absent in transplantable rat pituitary cell lines, so these analyses should provide new information about the regulatory role of these cells in the pituitary. The role of transforming growth factor beta (TGFbeta) in pituitary growth and differentiation will be investigated. Our preliminary studies indicate that estrogens down regulate and basic fibroblast growth factor (bFGF) up regulate TGFbeta1 mRNA in the normal pituitary gland in vitro and that TGFbeta1 inhibits cell proliferation in the GH3 cell line. In vitro and in vivo analyses with the GH3 cell line whose growth is stimulated by estrogen and with a pituitary cell line developed in our laboratory, the GHRH-CL1, whose growth is inhibited by estrogen will allow us to analyze the role of TGFbeta on pituitary cell growth and differentiation. We will use a cell line developed by targeted oncogenesis, alphaT3-1, as a model of gonadotroph tumors to learn more about cell proliferation and differentiation in gonadotroph cells and tumors. The chromogranin/secretogranin proteins and alpha subunit of glycoprotein hormones will be used as markers of differentiation in the analysis of nitric oxide synthase regulation in this cell line. The long term objectives of this study are to analyze the mechanisms by which hormones and growth factors influence proliferation and differentiation in pituitary tissues in order to learn more about the biology of normal and neoplastic pituitary cells. The data from these studies may lead to a better understanding of the development of pituitary neoplasms and may provide more effective means of treating these neoplasms.