IGFS AS REGULATORS OF ENDOCRINE CELL GROWTH & FUNCTION

我们将研究胰岛素样生长因子的作用 (IGFS)在控制小鼠生长和分化功能中的作用 来自两个内分泌腺，甲状腺和卵巢的细胞。它 是基于这样的假设，即IGFS既可以单独行动，也可以在 与组织特异性生长因子协调调节范围 许多细胞类型的生物学效应，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，IGF是“非特定”的增长因素。 它们单独作用，并与其他生长因子一起作用于 间充质起源，但具有高度特异性的营养激素 分化的细胞，如来自甲状腺和 卵巢。实验设计涉及到使用克隆的 维持甲状腺功能的甲状腺滤泡细胞系FRTL5 体外分化功能及其在生鲜食品中的应用 获得人卵巢颗粒细胞。世界银行的目标是 项目将是：1)鉴定细胞表面膜 FRTL5细胞上IGF-I、IGF-II和胰岛素受体 卵巢颗粒细胞；2)这些受体中的哪一个 介导型胰岛素样生长因子-I对这两种细胞的生物学效应 多克隆抗胰岛素受体血清型和A型 抗I型I型IGF受体的单抗(Alpha IR-3)； 研究IGFS与特定营养物质的相互作用 对于两种细胞类型中的每一种，TSH对 FRTL5细胞和颗粒细胞的FSH 生物活性；4)研究IFGs与 一系列其他组织生长因子在FRTL5细胞中的作用 探讨受体后的作用机制；5)研究 特异性原癌基因在FRTL5细胞中的表达 IGFS、PDGF和TSH；以及6)建立长期的 人卵巢颗粒细胞将适合于 研究细胞增殖和分化 功能。我们将探讨几个潜在的“第二信使” 途径包括IGF-I受体酪氨酸激酶和 腺苷环化酶系统。我们预计这些研究 将提供有关IGFS的作用的重要信息 在调节内分泌细胞生长和功能方面，关于 IGF刺激增殖性反应的机制 各种各样的细胞。

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.