SOMATOMEDIN AND INSULIN REGULATION OF THE PITUITARY

描述（改编自申请人的摘要）：经典 生长调节素假说指出IGFs介导许多生理性的 生长激素（GH）的作用。 然而，最近， 显然，IGF生理学在中枢神经系统中的不同， 与外周显著不同的是独特的或变异的IGF肽， 现在已经描述了CNS和CSF中的受体和结合蛋白。 一个新的生长调节素假说正在提出，这表明IGF 大脑中的一个网络构成了一个独特的系统，IGFs在其中发挥作用。 作为神经激素、神经调质和神经递质的重要作用。 这项提案的目的是阐明独特的生物化学的 研究IGF在垂体和CNS中的作用 physiology. 该项目的两个具体目标是解决 以下问题：一。CNS IGF的独特成分是什么 网络？： CNS IGF和胰岛素受体将通过 原位杂交和抗受体免疫组织化学 抗体的 新的CSF IGF结合蛋白将被纯化并进一步纯化。 的特点和结合蛋白在IGF行动的作用将是 评估。 胰岛素样生长因子及其受体的激素调节 将在大鼠中测定结合蛋白的合成。 浓度 胰岛素样生长因子肽的含量与胰岛素样生长因子mRNA丰度相关， 改变各种mRNA转录物的可翻译性的基因将被 问题研究 地方生产IGF-I和IGF-II的作用将是 测定 二. 体外和体内IGF-I和 IGF-II给药对下丘脑-垂体-IGF的调节 斧头？ IGF-I和IGF-II在GH和ACTH调节中的作用将 在静态和灌流培养中进行研究。 胃肠外效应 IGF-I和IGF-II对大鼠和人GH和IGF合成和分泌的影响 将被评估。 IGF-I和IGF-II对脑IGF受体的影响 并检测结合蛋白。 急性和慢性影响 IGF给药对葡萄糖稳态的影响将使用葡萄糖浓度来研究。 钳位技术

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.