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

该研究计划的最终目标是更好地了解控制哺乳动物卵巢和睾丸功能的生理因素。虽然我们目前知道生殖激素在性腺（卵巢和睾丸）中的作用，但其他局部产生的蛋白质的作用尚不完全清楚。在性腺中，一种被称为胰岛素样生长因子- i （IGF-I）的蛋白质被认为对精子和卵母细胞（卵子）的产生很重要，但它在这一过程中的实际作用尚不完全清楚。还有一组蛋白质叫做胰岛素样生长因子结合蛋白（igfbp），它们在组织中运输和维持igf - 1，但是，这些蛋白质是如何影响性腺功能的还没有完全阐明。再加上最近发现的一组蛋白酶可以灭活和降解igfbp，而所有这些生理因素相互作用使这些组织发挥功能的方式就更加不清楚了。转基因动物模型已被证明是生物学家更好地了解不同生物系统的有力工具。利用操纵DNA的技术，研究人员能够创造出动物模型，在这些模型中，感兴趣的基因可以被“关闭和打开”。利用这种技术，我们建议开发转基因小鼠模型，其中IGFBP基因可以被控制。通过研究这些基因的“开启和关闭”对这些模型性腺生理的影响，我们希望更好地理解激素、生长因子和结合蛋白是如何在正常功能的卵巢和睾丸中协同工作的。这项研究产生的知识将用于提高经济上重要的家养物种（如猪）的繁殖效率，并解决影响人类的各种疾病，包括不孕症和卵巢疾病。

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.