SOMATOMEDIN AND INSULIN REGULATION OF THE PITUITARY

描述(改编自申请人的摘要)：经典 生长抑素假说指出，IGFS在许多生理活动中起调节作用。 生长激素的功能。然而，最近，它已经成为 很明显，中枢神经系统中的IGF生理学不同 明显不同于外周作为独特或变异的IGF多肽， 受体和结合蛋白现在已经在中枢神经系统和脑脊液中被描述。 一种新的生长抑素假说被提出，该假说认为胰岛素样生长因子 大脑中的网络构成了IGFS发挥作用的独特系统 作为神经激素、神经调节剂和神经递质的重要角色。 这项提议的目的是阐明 中枢神经系统IGF网络及IGFS在垂体和中枢神经系统中的作用 生理学。该项目的两个具体目标是解决 以下问题：I.CNS IGF的独特组成部分是什么 网络？：中枢神经系统IGF和胰岛素受体将由 免疫组织化学、原位杂交和抗受体 抗体。新的脑脊液胰岛素样生长因子结合蛋白将被纯化并进一步 其特征和结合蛋白在IGF作用中的作用 评估过了。胰岛素样生长因子与胰岛素受体和胰岛素样生长因子的激素调节 结合蛋白的合成将在大鼠体内得到测定。浓缩度 IGF多肽的表达与IGF mRNA丰度相关，其影响因素 改变各种mRNA转录本的可译性的将是 学习。IGF-I和IGF-II的本地生产的作用将是 下定决心。IGF-I和IGF-I在体外和体内有什么作用？ 胰岛素样生长因子-II对下丘脑-垂体-胰岛素样生长因子的调节 斧头？胰岛素样生长因子-I和胰岛素样生长因子-II在生长激素和促肾上腺皮质激素意愿调节中的作用 在静态和灌流文化中进行研究。肠外营养的作用 胰岛素样生长因子-I和胰岛素样生长因子-II对大鼠和人生长激素和胰岛素样生长因子合成分泌的影响 将会被评估。IGF-I和IGF-II对脑内IGF受体的影响 并将检查结合蛋白。病毒的急性和慢性影响 胰岛素样生长因子对血糖动态平衡的影响将用葡萄糖来研究。 钳夹技术。

DESCRIPTION (adapted from the applicant's abstract): The classical somatomedin hypothesis states that the IGFs mediate many of the physiologic functions of growth hormone (GH). Recently, however, it has become apparent that IGF physiology in the central nervous system differs significantly from that in the periphery as unique or variant IGF peptides, receptors and binding proteins have now been described in the CNS and CSF. A new somatomedin hypothesis is being proposed which suggests that the IGF network in the brain constitutes a distinct system in which the IGFs play important roles as neurohormones, neuromodulators and neurotransmitters. The goal of this proposal is to elucidate the unique biochemistry of the CNS IGF network and to study the role of IGFs in pituitary and CNS physiology. The two specific aims of the project are to address the following questions: I. What are the unique components of the CNS IGF Network?: CNS IGF and insulin receptors will be localized by immunohistochemistry, by in situ hybridization and by antireceptor antibodies. The novel CSF IGF binding protein will be purified and further characterized and the role of binding proteins in IGF action will be assessed. The hormonal regulation of IGF and insulin receptor and IGF binding protein synthesis will be determined in the rat. The concentration of IGF peptide will be correlated with IGF mRNA abundance, and the factors which alter translatability of the various mRNA transcripts will be studies. The role of local production of IGF-I and IGF-II will be determined. II. What are the effects of in vitro and in vivo IGF-I and IGF-II administration on the regulation of the hypothalamic-pituitary-IGF axes? The role of IGF-I and IGF-II in the regulation of GH and ACTH will be studied in static and perifusion cultures. The effect of parenteral IGF-I and IGF-II on GH and IGF synthesis and secretion in the rat and human will be evaluated. The effect of IGF-I and IGF-II on brain IGF receptors and binding proteins will be examined. The acute and chronic effects of IGF administration on glucose homeostasis will be studied using the glucose clamp technique.