Remodeling of mammary tissue and lactation persistency

本研究计划的长期目标是开发一种经济上可行且消费者可接受的技术，以提高奶牛的泌乳持久性，延长泌乳时间。从乳腺的角度来看，产奶量只是分泌细胞数量和这些细胞分泌活性的函数。在山羊中，分泌细胞的减少是导致泌乳减少的原因。现在已经在啮齿类动物和反刍动物中证实，在哺乳期的乳腺细胞损失是通过程序性细胞死亡（细胞凋亡）发生的。细胞凋亡也发生在泌乳后期，并解释了泌乳下降过程中分泌细胞的逐渐丧失。因此，有相当大的动机来确定调节乳腺细胞凋亡的因素，特别是在这些早期阶段的逐渐退化。我的假设是：通过降低乳腺细胞死亡率来降低产奶量下降的速度是可能的；-泌乳诱导的PRL释放对维持乳腺上皮细胞的分化和存活具有重要意义；-斯坦钙素降低细胞内Ca2+水平，从而减少牛奶成分的合成。我的短期目标是：1-评估不同泌乳下降率奶牛STC的凋亡、细胞增殖和表达。影响泌乳率下降的因素有胎次、妊娠和限饲。2-确定钙稳态在控制乳腺功能中的作用3-确定挤奶诱导泌乳素释放对泌乳持续性的作用。在泌乳素释放抑制剂抑制泌乳素释放的奶牛中，将在8周内评估泌乳下降率、基因表达和细胞凋亡。4-确定控制泌乳素释放量的因素

The long range objective of this research program is to develop an economically viable and consumer acceptable technology that would improve lactation persistency and enable longer lactation in dairy cows. From a mammary gland perspective, milk production is simply a function of the number of secretory cells and the secretory activity of these cells.  In goats,   it is the loss of secretory cells which accounts for the decrease in milk yield during declining lactation.  It is now well established in rodents and ruminants that mammary cell loss during involution (termination of lactation) occurs through programmed cell death (apoptosis).  Apoptosis also occurs in late lactation and accounts for the progressive loss of secretory cells in declining lactation.  Therefore, there are considerable incentives to identify the factors that regulate mammary apoptosis, in particular during these early stages of gradual involution.My hypotheses are:-It is possible to reduce the rate of decline in milk production by reducing the rate of mammary cell death;-The milking-induced PRL release is important to maintain the differentiation and the survival of the mammary epithelial cells;-Stanniocalcin reduces intracellular level of Ca2+ which reduce synthesis of milk component.My short range objectives are:1- To evaluate apoptosis, cell proliferation and expression of STC in cows with different rates of lactation decline. Factors affecting rate of  lactation decline will be parity, pregnancy and feed restriction.  2- To determine the role of calcium homeostasis in the control of mammary gland functions 3- To determine the role of milking induce release of prolactin on lactation persistency. Rate of lactation decline, gene expression, and cell apoptosis will be evaluated in cows where prolactin release will be prevented during 8 weeks by administration of an inhibitor of prolactin release.4- To determine the factors controling the magnitude of milking-induced release of prolactin