IGFS AS REGULATORS OF ENDOCRINE CELL GROWTH & FUNCTION

IGFS 作为内分泌细胞生长的调节剂

• 批准号: 3236672
• 负责人: MITCHELL T RABKIN
• 金额: $ 15.48万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 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 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3236672
• 关键词: adenylate cyclase; cell differentiation; cell growth regulation; cell membrane; cyclic AMP; epithelium; follicle stimulating hormone; gene expression; graafian follicles; growth factor; growth factor receptors; hormone regulation /control mechanism; human tissue; insulin; insulin receptor; insulinlike factor; laboratory mouse; luteinizing hormone; monoclonal antibody; progesterone; protein tyrosine kinase; protooncogene; radioimmunoassay; receptor coupling; second messengers; thyroid gland; thyrotropin; tissue /cell culture

We will investigate the role of insulin-like growth factors (IGFs) in the control of growth and differentiated function in cells from two endocrine glands, the thyroid and the ovary. It is based on the hypothesis that IGFs act both alone and in concert with tissue specific growth factors to regulate a range of biological effects in many cell types, including those with highly specialized funciton, i.e., differentiated endocrine epithelial cells. Thus, IGFs are "non-specific" growth factors that act alone and with other growth factors in cells of mesenchymal origin but with specific trophic hormones in highly differentiated cells such as those from the thyroid and the ovary. The experimental design involves the use of a cloned line of thyroid follicular cells, FRTL5, that maintains thyroid differentiated function in vitro and the use of freshly obtained human ovarian granulosa cells. The goals of the project will be to: 1) identify the cell-surface membrane receptors for IGF-I, IGF-II, and insulin on FRTL5 cells and ovarian granulosa cells; 2) probe which of these receptors mediate IGF-I stimulated biological effects in these two cells types with polyclonal anti-insulin receptor sera and a monoclonal anti-type I IGF receptor antibody (Alpha IR-3); 3) investigate the interactions of IGFs with the specific trophic pituitary hormones for each of the two cell types, TSH for FRTL5 cells and FSH for the granulosa cells, over a range of biological activities; 4) study the interaction of IFGs with a series of other tissue growth factors in FRTL5 cells as a means of probing post-receptor mechanisms of action; 5) study specific protooncogene expression in FRTL5 cells in response to IGFs, PDGF, and TSH; and 6) establish long-term cultures of human ovarian granulosa cells that will be suitable for studying cellular proliferation as well as differentiated function. We will probe several potential "second messenger" pathways including the IGF-I receptor tyrosine kinase and the adenylate cyclase system. We anticipate that these studies will provide important information both about the role of IGFs in regulating endocrine cell growth and function and about the mechanisms by which IGFs stimulate a proliferative response in a wide variety of cells.

我们将研究胰岛素样生长因子的作用 （IGFs）在控制生长和分化功能中的作用 细胞来自两个内分泌腺，甲状腺和卵巢。 它 是基于这样的假设，即IGFs单独作用， 与组织特异性生长因子协同作用， 许多细胞类型的生物效应，包括那些 高度专业化的功能，即，分化的内分泌 上皮细胞 因此，IGFs是“非特异性”生长因子 单独或与其他生长因子共同作用于 间充质起源，但与特定的营养激素在高度 分化的细胞，如来自甲状腺和 卵巢 实验设计涉及使用克隆的 甲状腺滤泡细胞系，FRTL 5，维持甲状腺 体外分化功能和使用新鲜的 获得人卵巢颗粒细胞。 的目标 项目将：1）识别细胞表面膜 FRTL 5细胞上IGF-I、IGF-II和胰岛素的受体， 卵巢颗粒细胞; 2）探测这些受体中的哪一种 介导IGF-I刺激这两种细胞的生物学效应 型与多克隆抗胰岛素受体血清和 单克隆抗I型IGF受体抗体（α IR-3）; 3） 研究胰岛素样生长因子与特定营养物质的相互作用 两种细胞类型中的每一种的垂体激素， FRTL 5细胞和颗粒细胞的FSH，在一定范围内， 生物活性; 4）研究IFG与 FRTL 5细胞中的一系列其他组织生长因子作为手段 探索受体后作用机制; 5）研究 FRTL 5细胞中特异性原癌基因表达 IGF、PDGF和TSH;以及6）建立 人卵巢颗粒细胞，其将适合于 研究细胞增殖和分化 功能 我们将探索几个潜在的“第二信使” 途径，包括IGF-I受体酪氨酸激酶和 腺苷酸环化酶系统。 我们预计这些研究 将提供有关IGFs作用的重要信息， 调节内分泌细胞的生长和功能， IGFs刺激细胞增殖反应的机制 各种各样的细胞