STUDIES OF NORMAL AND NEOPLASTIC HUMAN PITUITARY TISSUE

正常人和肿瘤患者激素分泌的调节 将对脑下垂体组织进行形态学研究， 免疫组织化学和生化方法。的形态研究 光镜和电子显微镜水平和免疫组织化学方法 针对垂体激素和嗜铬粒蛋白的抗体将用于 正常脑垂体、催乳素(PRL)和空细胞的特征 (未分化)腺瘤。雌激素，溴隐亭， 促甲状腺激素释放激素，促性腺激素释放激素，花生四烯酸 酸性和佛波酯对催乳素释放和多巴胺受体结合的影响 将在体外和超微结构免疫组织化学中进行研究。这个 垂体腺垂体催乳素信使RNA生物合成的调控 细胞将通过原位杂交进行检测，使用合成的 寡核苷酸探针。反向溶血空斑试验检测 单细胞产生的激素将被用于研究 催乳素和生长激素(GH)对正常和肿瘤垂体腺的影响 细胞。初步研究表明，培养的产生催乳素的腺瘤 在我们的培养系统中，细胞对各种促分泌剂做出反应，这些 反之，肿瘤通常同时产生催乳素和生长激素。 溶血空斑分析，虽然通常的免疫组织化学方法 通常无法在同一肿瘤中同时检测到催乳素和生长激素的产生。 已经检测到显著水平的多巴胺受体结合在四个 在死后3小时内检查过的正常脑垂体。我们 已经表明，大多数空细胞腺瘤可以被描述为 用单抗免疫反应进行免疫组织化学 对抗我们实验室开发的嗜铬粒蛋白。这项建议 旨在了解形态和生物化学的差异 人正常脑下垂体组织与肿瘤组织的相似性 对正常和肿瘤垂体细胞的生物学有更多的了解。

The regulation of hormone production in normal and neoplastic human pituitary gland tissues will be investigated using morphological, immunohistochemical and biochemical methods. Morphological studies at the light and electron microscope level and immunohistochemical methods with antibodies against pituitary hormones and chromogranin will be used to characterize normal pituitaries, prolactin (PRL) and null cell (undifferentiated) adenomas. The effects of estrogens, bromocriptine, thyrotropin releasing hormone, gonadotropin releasing hormone, arachidonic acid and phorbol esters on PRL release and on dopamine receptor binding will be studied in vitro and by ultrastructural immunohistochemistry. The regulation of the biosynthesis of PRL messenger RNA in culture pituitary cells will be examined by in situ hybridization using synthetic oligonucleotide probes. The reverse hemolytic plaque assay which detects hormone production by single cells will be used to study the production of PRL and growth hormone (GH) by the same normal and neoplastic pituitary cells. Preliminary studies have shown that cultured PRL-producing adenoma cells respond to various secretagogues in our culture system and that these tumors are often producing both PRL and GH as detected by the reverse hemolytic plaque assay, although the usual immunohistochemical methods often fail to detect both PRL and GH production in the same tumor. Significant levels of dopamine receptor binding have been detected in four normal pituitaries which have been examined within 3 hours post mortem. We have shown that most null cell adenomas can be characterized immunohistochemically by immunoreactivity with a monoclonal antibody against chromogranin which was developed in our laboratory. This proposal is designed to understand the morphological and biochemical differences and similarities betwen normal and neoplastic human pituitary tissues and to gain more insight into the biology of normal and neoplastic pituitary cells.