Regulation of mammary physiology by IGF-IR

IGF-IR 对乳腺生理的调节

• 批准号: 250648-2009
• 负责人: Moorehead, Roger
• 金额: $ 2.04万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=426403
• 关键词: Regulation; mammary; physiology; IGF; IR

The overall goal of this research is to understand the role of the type I insulin-like growth factor receptor (IGF-IR) in mammary physiology. The IGF-IR is the main signaling receptor mediating the effects of the two insulin-like growth factor (IGF) ligands, IGF-I and IGF-II. Until now, an in vivo model where the levels of the IGF-IR can be manipulated in the mammary gland did not exist. My lab has created a mouse model where the levels of IGF-IR can be overexpressed or returned to normal through the addition or withdrawal of doxycycline from the animals food supply. With this model the levels of IGF-IR can be increased at discrete physiologic stages of the mammary gland such as development, lactation and involution and the effects of IGF-IR overexpression on these process can be determined. The reason this type of study is important is that bovine somatotrophin (bST), also know as bovine growth hormone, has been used in dairy cattle to increase milk production for years. Growth hormone mediates a number of its effects by increasing IGF signaling. Therefore, our studies will determine whehter growth hormones effects in the mammary gland are mediate via IGF-IR signaling and whether enhancing IGF-IR signaling can replace growth hormone and directly promote milk production. Using this knowledge of IGF signaling we may eventually identify proteins or signaling networks that are more efficient and effective at promoting milk production in dairy cattles that bST.

本研究的总体目标是了解I型胰岛素样生长因子受体（IGF-IR）在乳腺生理学中的作用。IGF-IR是介导两种胰岛素样生长因子（IGF）配体IGF-I和IGF-II的作用的主要信号受体。到目前为止，在体内模型中的IGF-IR的水平可以在乳腺中操纵不存在。我的实验室已经建立了一个小鼠模型，其中IGF-IR的水平可以通过添加或从动物食物供应中撤出强力霉素来过度表达或恢复正常。利用该模型，IGF-IR的水平可以在乳腺的离散生理阶段（例如发育、泌乳和退化）增加，并且可以确定IGF-IR过表达对这些过程的影响。这种类型的研究之所以重要，是因为牛生长激素（bST），也称为牛生长激素，多年来一直用于奶牛以增加牛奶产量。生长激素通过增加IGF信号传导介导其许多作用。因此，我们的研究将确定生长激素在乳腺中的作用是否通过IGF-IR信号传导介导，以及增强IGF-IR信号传导是否可以取代生长激素并直接促进产奶量。利用IGF信号的这一知识，我们可能最终确定蛋白质或信号网络，更有效地促进奶牛的牛奶生产，BST。