STUDIES OF NORMAL AND NEOPLASTIC HUMAN PITUITARY TISSUE

正常人和肿瘤患者激素分泌的调节 将使用形态学， 免疫组化和生化方法。 形态学研究 光镜、电镜及免疫组化方法， 抗垂体激素和嗜铬粒蛋白的抗体将用于 表征正常垂体、催乳素（PRL）和空细胞 （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 酸和佛波酯对PRL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研究。 的 垂体催乳素信使RNA合成的调控 细胞将通过原位杂交使用合成的 寡核苷酸探针。 反向溶血空斑试验检测 单细胞的激素生产将用于研究 PRL和生长激素（GH）由相同的正常和肿瘤垂体 细胞 初步研究表明，培养的PRL分泌腺瘤 细胞对我们培养系统中的各种促分泌素有反应， 肿瘤通常同时产生PRL和GH，如通过逆转录病毒检测到的。 溶血空斑试验，虽然通常的免疫组织化学方法 通常不能检测同一肿瘤中PRL和GH的产生。 多巴胺受体结合的显着水平已被检测到在四个 在死后3小时内检查的正常垂体。 我们 已经表明，大多数空细胞腺瘤的特点是 通过与单克隆抗体的免疫反应性进行化学分析 对抗我们实验室开发的嗜铬粒蛋白。 这项建议 旨在了解形态和生化差异， 正常和肿瘤性人类垂体组织之间的相似性， 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.