GALANIN IN PITUITARY ADENOMAS

垂体腺瘤中的甘丙肽

• 批准号: 2145208
• 负责人: JAMES F HYDE
• 金额: $ 10.27万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2145208
• 关键词: adenoma; antiserum; cell cycle; cell type; disease /disorder model; epidermal growth factor; estrogen receptors; estrogens; fibroblast growth factor; galanin; hormone regulation /control mechanism; hormone related neoplasm /cancer; laboratory mouse; laboratory rat; messenger RNA; neoplastic growth; neuropeptides; neurotrophic factors; peptide hormone biosynthesis; pituitary gland; pituitary neoplasms; prolactin releasing /inhibiting factor

This proposal tests the hypothesis that the peptide galanin plays a significant role in pituitary adenoma formation. The majority of pituitary adenomas in humans secrete copious amounts of prolactin. Hyperprolactinemia is the leading cause of neuroendocrine-related infertility in women and impotence in men. Estrogen has a profound stimulatory effect on prolactin synthesis and release. and induces prolactinoma formation in the rat. In addition to its effects on prolactin, estrogen markedly increases the synthesis of galanin in the anterior pituitary gland. Galanin is stored with prolactin in the same secretory granules of estrogen-treated pituitary cells, and its secretion is regulated by the same hypothalamic hormones. Galanin is the first anterior pituitary peptide, in addition to the "classic" pituitary hormones, whose secretion is controlled by hypothalamic factors. In Specific Aim 1 the direct effects of galanin on pituitary cell proliferation will be examined in vitro and in vivo. The effects of galanin on 3H-thymidine incorporation into DNA will be assessed in conjunction with immunocytochemistry to identify which pituitary cell types are proliferating. Moreover, galanin antiserum will be administered in vivo to determine if estrogen-induced pituitary tumor formation is inhibited by passive immunization. Specific Aim 2 will address the hypothesis that galanin is one of the factors which contributes to the heterogeneity of prolactin secretion from hyperplastic lactotrophs. These studies will utilize adenomatous pituitary cells and combine the reverse hemolytic plaque assay for prolactin release with immunocytochemistry for galanin to assess if lactotrophs which colocalize galanin hypersecrete prolactin. Specific Aim 3 is designed to determine if estrogen and selected growth factors directly regulate galanin within pituitary cells. First, double-labeling immunocytochemistry for estrogen receptors and galanin will used to determine if galanin-containing pituitary cells are direct targets of estrogen. Second, the effects of estrogen and other growth factors on galanin release and mRNA levels will be tested in vitro. Specific Aim 4 will examine if galanin synthesis and release are increased in pituitary adenomas which are induced by factors other than estrogen. Specifically, animal models of mammosomatotroph and thyrotroph adenomas will be studied. Overall, these studies will determine the role of galanin in tumorigenesis in the pituitary gland, and provide insight to the physiology and pathophysiology of galanin.

这项提议验证了甘丙肽在脑内起作用的假设。 在垂体腺瘤形成中起重要作用。 大多数 人类的垂体腺瘤分泌大量的催乳素。 高催乳素血症是神经内分泌相关性 女性不孕和男性阳痿。 雌激素有着深刻的 对催乳素合成和释放的刺激作用。并诱导 催乳素瘤的形成。 除了影响 催乳素，雌激素显着增加甘丙肽的合成， 垂体前叶 甘丙肽与催乳素一起储存在 雌激素处理的垂体细胞分泌颗粒及其分泌 都是由相同的下丘脑激素调节的 甘丙肽是第一个 垂体前叶肽，除了“经典”垂体 激素，其分泌受下丘脑因素控制。 在 具体目的1甘丙肽对垂体细胞的直接作用 将在体外和体内检查增殖。 的影响 甘丙肽对3 H-胸苷掺入DNA的影响将在 结合免疫细胞化学来鉴定哪种垂体细胞 类型正在激增。 此外，甘丙肽抗血清将 体内给药，以确定雌激素诱导的垂体瘤 通过被动免疫抑制形成。 具体目标2将 解决了甘丙肽是导致 促进了泌乳素分泌的异质性， 催乳素 这些研究将利用腺瘤性垂体细胞， 联合收割机将催乳素释放的反向溶血空斑试验与 甘丙肽免疫细胞化学以评估是否共定位的催乳素 甘丙肽分泌过多的催乳素。 具体目标3旨在确定 如果雌激素和选择的生长因子直接调节甘丙肽， 垂体细胞 首先，雌激素的免疫细胞化学双标记 受体和甘丙肽将用于确定是否含有甘丙肽 垂体细胞是雌激素的直接靶细胞。 第二，影响 雌激素和其他生长因子对甘丙肽释放和mRNA水平的影响将 在体外测试。 具体目标4将检查甘丙肽的合成和 在垂体腺瘤中， 除了雌激素。 具体而言，乳房生长激素的动物模型和 将研究促甲状腺细胞腺瘤。 总的来说，这些研究将 确定甘丙肽在脑垂体肿瘤发生中的作用， 并为甘丙肽的生理学和病理生理学提供见解。