Regulation of mammary physiology by IGF-IR

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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.