REGULATION OF RAT PITUITARY HYPERPLASIA AND NEOPLASIA

催乳素细胞增生性疾病的发生发展及临床意义 转化为产生催乳素的肿瘤垂体腺 肿瘤的研究将在大鼠身上使用形态学， 免疫组织化学和生化方法。形态 以及光和电子的免疫组织化学研究 微观水平将用来描述不同的亚型 催乳素细胞和乳腺癌细胞(它们产生了 催乳素和生长激素)在增生性疾病和 肿瘤性MTTW15和MTTF4组织。的功能 正常、增生性和非增生性垂体腺泡星状细胞 将对肿瘤性脑垂体进行调查 免疫组织化学和超微结构研究。的作用 调节催乳素分泌的S100蛋白将 调查过了。初步研究表明，S100蛋白 哪种物质存在于垂体滤泡星状细胞中可以刺激 体外释放催乳素表明这些细胞可能 催乳素释放的旁分泌型调节。丰富 肿瘤催乳素、生长激素和 增生性变乳房和毛囊星状细胞 垂体腺将通过单位速度沉淀法制备。 重力和密度梯度离心法。这些浓缩的细胞 种群将被用于研究催乳素的体外释放和 分析多巴胺和雌激素受体在相对 均一的细胞群体。最近的研究表明， 雌激素抑制可移植的MTT/W15和 四甲基偶氮唑蓝/F4并同时促进垂体瘤生长 MTT/W15肿瘤细胞的激素分泌。我们计划将其用于 原位和细胞质斑点杂交分析 定量测定生长激素和催乳素信使的变化 雌激素诱导的肿瘤细胞生长抑制过程中的RNA。 雌激素和多巴胺在调节其受体功能中的作用 垂体瘤发生过程中的受体将是 通过研究受体水平的变化来分析 从增生性变到瘤性。这样做的目的是 研究是1)更清楚地定义形态和 增生性和肿瘤性垂体的生化特征 组织，2)分析卵泡星状细胞和S100的作用 蛋白质调节催乳素细胞的增殖和退化 自主性肿瘤的生长，3)分析 垂体瘤中雌激素、多巴胺及其受体的研究 开发和4)开发更精细和具体的方法 催乳素和生长激素的调节分析 增生性和肿瘤性疾病细胞水平的生物合成 脑下垂体。

The development of prolactin cell hyperplasia and the transformation to neoplastic prolactin producing pituitary tumors will be investigated in rats using morphological, immunohistochemical and biochemical methods. Morphological and immunohistochemical studies at the light and electron microscopic levels will be used to characterize various subtypes of prolactin cells and mammosomatotropic cells (which produced both prolactin and growth hormone) in hyperplastic and neoplastic MtT/W15 and MtT/F4 tissues. The functions of the pituitary folliculostellate cells in normal, hyperplastic and neoplastic pituitaries will be investigated by immunohistochemical and ultrastructural studies. The role of S100 protein in regulating prolactin secretion will be investigated. Preliminary findings indicate that S100 protein which is present in pituitary folliculo-stellate cells can stimulate prolactin releases in vitro suggesting that these cells may exert a paracrine type regulation of prolactin release. Enriched populations of neoplastic prolactin, growth hormone and mammosmatotropic and folliculo-stellate cells from hyperplastic pituitaries will be prepared by velocity sedimentation at unit gravity and density gradient centrifugation. These enriched cell populations will be used to study prolactin release in vitro and to analyze dopamine and estrogen receptors in relatively homogeneous cell population. Recent studies have shown that estrogens inhibit the growth of transplantable MtT/W15 and MtT/F4 pituitary tumors and concurrently increases growth hormone production by the MtT/W15 tumor. We plan to use in situ and cytoplasmic dot blot hybridization to analyze and quantitate changes in growth hormone and prolactin messenger RNA in tumor cells during estrogen-induced growth-inhibition. The role of estrogen and dopamine in the regulation of their receptors during development of pituitary tumors will be analyzed by studying changes in receptor levels during transformation from hyperplasia to neoplasia. The goals of this study are 1) to define more clearly the morphological and biochemical features of hyperplastic and neoplastic pituitary tissues, 2) analyze the role of folliculostellate cells and of S100 protein is regulating prolactin cell hyperplasia and regression and the growth of autonomous tumors, 3) analyze the role of estrogen and dopamine and their receptors in pituitary tumor development and 4) develop more refined and specific methods to analyze the regulation of prolactin and growth hormone biosynthesis at the cellular level in hyperplastic and neoplastic pituitaries.