Regulation of mammary physiology by IGF-IR

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作用的主要信号受体。到目前为止，还不存在可以在乳腺中操纵IGF-IR水平的体内模型。我的实验室已经建立了一个小鼠模型，在这个模型中，通过在动物饲料中添加或停用多西环素，IGF-IR的水平可以过度表达或恢复正常。该模型可以在乳腺发育、哺乳期和退化期等不同的生理阶段增加IGF-IR的水平，并可以确定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)，也被称为牛生长激素，多年来一直被用于增加奶牛的产奶量。生长激素通过增加IGF信号来调节其一系列效应。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信号介导，以及增强IGF-IR信号是否可以取代生长激素直接促进产奶量。利用IGF信号转导的知识，我们最终可能识别出比BST更有效和更有效地促进奶牛产奶量的蛋白质或信号网络。

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.