GALANIN IN PITUITARY ADENOMAS

垂体腺瘤中的甘丙肽

• 批准号: 2145207
• 负责人: JAMES F HYDE
• 金额: $ 9.76万
• 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/2145207
• 关键词: adenoma; antiserum; autoradiography; cell cycle; cell type; disease /disorder model; epidermal growth factor; estrogen receptors; estrogens; fibroblast growth factor; hormone regulation /control mechanism; hormone related neoplasm /cancer; immunocytochemistry; laboratory mouse; laboratory rat; messenger RNA; neoplastic growth; neuropeptides; neurotrophic factors; northern blottings; passive immunization; peptide hormone biosynthesis; pituitary gland; pituitary neoplasms; prolactin releasing /inhibiting factor; southern blotting; tissue /cell culture

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.

该提案检验了肽甘氨酸扮演的假设 在垂体腺瘤形成中的重要作用。 大多数 人类中的垂体腺瘤分泌大量的催乳素。 高泌乳素血症是神经内分泌相关的主要原因 女性不孕症和男性无能为力。 雌激素有深刻的 对催乳素合成和释放的刺激作用。和诱导 大鼠的催乳瘤形成。 除了对 催乳素，雌激素明显增加了加拉宁的合成 前垂体。 加拉宁与催乳素一起存储在同一 雌激素处理的垂体细胞的分泌颗粒及其分泌物 受同一下丘脑激素调节。 加拉宁是第一个 垂体前肽，除了“经典”垂体 激素，其分泌由下丘脑因素控制。 在 特定目标1加拉宁对垂体细胞的直接影响 将在体外和体内检查增殖。 效果 将在3H-胸苷上掺入DNA上的Galanin将在 与免疫细胞化学结合以识别哪种垂体细胞 类型正在增殖。 此外，加拉宁抗血清将是 在体内施用以确定雌激素诱导的垂体肿瘤是否 被动免疫抑制了形成。 具体目标2将 解决了加拉宁是一个因素之一 有助于增生性催乳素分泌的异质性 乳营养素。 这些研究将利用腺瘤垂体细胞和 将反向溶血斑块测定法与催乳素释放与 加拉宁的免疫细胞化学化学，以评估乳腺营养的乳酸化学能力化学 加拉宁超催乳素。 特定目标3旨在确定 如果雌激素和选定的生长因子直接调节加拉宁 垂体细胞。 首先，雌激素的双标记免疫细胞化学 受体和加拉蛋白将用于确定是否含甘氨酸 垂体细胞是雌激素的直接靶标。 第二，影响 Galanin释放和mRNA水平的雌激素和其他生长因子将 在体外进行测试。 具体目标4将检查加拉宁合成和 垂体腺瘤中的释放增加了，这是由因素诱导的 除了雌激素。 具体而言，乳腺营养的动物模型和 将研究甲状腺营养腺瘤。 总体而言，这些研究将 确定加拉蛋白在垂体中肿瘤发生中的作用， 并洞悉加拉宁的生理学和病理生理学。