STUDIES OF NORMAL AND NEOPLASTIC HUMAN PITUITARY TISSUE

正常和肿瘤性人类垂体组织的研究

• 批准号: 3184715
• 负责人: Ricardo Vincent Lloyd
• 金额: $ 12.19万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184715
• 关键词: adenoma; arachidonate; biopsy; bromocriptine; dopamine receptor; electron microscopy; endocrine pharmacology; estrogens; gonadotropin releasing factor; histochemistry /cytochemistry; hormone related neoplasm /cancer; human tissue; hypothalamic pituitary axis; immunochemistry; in situ hybridization; monoclonal antibody; neoplastic cell; nucleic acid probes; phorbols; pituitary gland; pituitary neoplasms; plaque assay; postmortem; prolactin; radioimmunoassay; radiotracer; somatostatin; thyrotropin releasing hormone; tissue /cell culture

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.

正常和肿瘤人中激素产生的调节 垂体组织将使用形态学， 免疫组织化学和生化方法。 形态学研究 光和电子显微镜水平和免疫组织化学方法 针对垂体激素和染色体素的抗体将用于 表征正常的垂体，催乳素（PRL）和无效细胞 （未分化）腺瘤。 雌激素，溴o我的作用， 甲状腺激素释放激素，促性腺激素释放激素，花生四角 PRL释放和多巴胺受体结合时的酸和佛波酯 将在体外和超微结构免疫组织化学上进行研究。 这 培养垂体中PRL信使RNA的生物合成调节 将使用合成的原位杂交检查细胞 寡核苷酸探针。 检测到的反向溶血斑块测定 单细胞产生激素将用于研究 PRL和生长激素（GH）通过相同的正常和肿瘤垂体 细胞。 初步研究表明，培养的PRL产生腺瘤 细胞对我们的文化系统中的各种促分子做出反应，这些 反向检测到的肿瘤通常会产生PRL和GH 溶血斑块测定，尽管通常是免疫组织化学方法 通常无法在同一肿瘤中检测到PRL和GH的产生。 在四个 尸体后3小时内检查的正常垂体。 我们 已经表明大多数无效细胞腺瘤可以被表征 通过单克隆抗体免疫反应性免疫组织化学 反对在我们的实验室中开发的染色体素。 这个建议 旨在了解形态学和生化差异以及 在正常和肿瘤的人垂体组织中的相似性 对正常和肿瘤垂体细胞的生物学有了更多的了解。