The role of insulin-like growth factors and their binding proteins in gametogenesis

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The ultimate goal of the proposed research program is to develop a better understanding of the physiological factors controlling ovarian and testicular function in mammals. Although we are currently aware of the role that reproductive hormones play in the gonads (ovaries and testes), the purpose of other locally produced proteins is not fully understood.  In the gonads, a protein referred to as Insulin-like growth factor-I (IGF-I) is considered to be important for the production of sperm and oocytes (eggs) but its actual role in this process is not completely clear. There is also another group of proteins called Insulin-like growth factor binding proteins (IGFBPs) that transport and maintain IGF-I in the tissue, but again, how these proteins actually affect gonad function has not yet been fully elucidated. Add to this the recent discovery of a group of proteases that inactivate and degrade IGFBPs and the manner in which all these physiological factors interact to make these tissues function is even more unclear.  Genetically modified animal models have proven to be a powerful tool for biologists to better understand different biological systems.   Using techniques to manipulate DNA, researchers are able to create animal models in which genes of interest can be turned "off and on".  Employing this type of technology we propose to develop genetically modified mouse models in which the IGFBP genes can be controlled.   By studying the effect of turning these genes "off and on" on the gonad physiology of these models, we hope to better understand how hormones, growth factors and binding proteins work in unison in a normally functioning ovary and testis.  Knowledge generated from this research will be used to improve the reproductive efficiency of economically important domestic species, such as swine, and address various conditions affecting the human population, including infertility and ovarian disease.