SOMATOMEDIN AND INSULIN REGULATION OF THE PITUITARY

垂体生长调节素和胰岛素的调节

• 批准号: 2139706
• 负责人: ANDREW R HOFFMAN
• 金额: $ 19.15万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2139706
• 关键词: adrenocorticotropic hormone; carbohydrate balance; central nervous system; genetic translation; glucose metabolism; growth factor receptors; hormone binding protein; hormone regulation /control mechanism; human subject; hypothalamic pituitary axis; immunocytochemistry; in situ hybridization; insulin receptor; insulinlike growth factor; laboratory rat; neuroendocrine system; neurohormones; neurotransmitters; peptide hormone biosynthesis; perfusion; pituitary gland; somatotropin; tissue /cell culture

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.

描述（改编自申请人的摘要）：经典 躯干素假设指出，IGF介导了许多生理学 生长激素（GH）的功能。 但是最近，它已经变成了 显然，中枢神经系统中的IGF生理学有所不同 在外围中，它是独特或变体的IGF肽的显着， 现在已经在中枢神经系统和CSF中描述了受体和结合蛋白。 提出了一种新的母系假设，这表明IGF 大脑中的网络构成了IGF播放的独特系统 作为神经激素，神经调节剂和神经递质的重要作用。 该提议的目的是阐明 CNS IGF网络并研究IGF在垂体和CNS中的作用 生理。 该项目的两个具体目的是解决 以下问题：I。CNS IGF的独特组成部分是什么 网络？：CNS IGF和胰岛素受体将由 免疫组织化学，通过原位杂交和抗受体 抗体。 新型的CSF IGF结合蛋白将被纯化，并进一步 表征和结合蛋白在IGF作用中的作用将是 评估。 IGF和胰岛素受体和IGF的激素调节 结合蛋白合成将在大鼠中确定。 浓度 IGF肽的含量将与IGF mRNA丰度相关，这些因素 各种mRNA转录本的可改变翻译性将是 研究。 IGF-I和IGF-II本地生产的作用将是 决定。 ii。 体外和体内IGF-I和 IGF-II给药下丘脑 - 垂体-IGF的调节 轴？ IGF-I和IGF-II在GH和ACTH调节中的作用将 在静态和炎症培养物中进行研究。 肠胃外的影响 大鼠和人类的GH和IGF合成和分泌的IGF-I和IGF-II 将进行评估。 IGF-I和IGF-II对脑IGF受体的影响 将检查结合蛋白。 急性和慢性影响 将使用葡萄糖来研究葡萄糖稳态的IGF给药 夹具技术。