Remodeling of mammary tissue and lactation persistency

该研究项目的长期目标是提高我们对乳腺退化控制的生物学过程的认识，并开发经济上可行、消费者可接受的技术或实践，以提高奶牛的泌乳持久性，延长泌乳时间。延长泌乳期会减少奶牛在泌乳早期的寿命比例，从而减少与此相关的疾病、代谢紊乱和繁殖失败的发生。***虽然对持久性的生物控制知之甚少，但挤奶频率、泌乳完整度、胎次、光周期、营养摄入和妊娠期等因素已被证明会影响持久性。最近在我的实验室进行的工作表明，与人们所认为的相反，泌乳素（PRL）激素在乳反刍动物中具有乳糖生成作用。如果PRL的基础水平与产奶量没有明显的相关性，那么挤奶诱导的PRL释放与产奶量相关。在啮齿类动物的乳腺中已经报道了PRL的抗凋亡作用，因此，我们发现PRL分泌被抑制的奶牛的腺体中凋亡更多。因此，PRL，尤其是泌乳诱导的PRL，可能通过限制细胞损失和维持细胞分化而成为持续泌乳的重要因素。然而，我们也发现PRL在乳腺水平上的促乳作用是通过一种机制来调节的，这种机制仍有待阐明。******我的假设是：***-泌乳诱导的激素释放对维持乳腺上皮细胞的分化、分泌活性和存活至关重要。***-有几个因素通过调节泌乳时激素的释放量和/或乳腺对激素的反应来影响产奶量和泌乳持续性。******我的短期目标是：***1-确定控制泌乳诱导PRL释放量的因素***2-确定局部因素影响泌乳持续性的机制。***3-确定系统因素影响泌乳持续性的机制

The long range objectives of this research program are to improve our knowledge of the biological process involved in the control of mammary gland involution and to develop economically viable and consumer acceptable technologies or practices that would improve lactation persistency and enable longer lactation in dairy cows. Extended lactation would reduce the proportion of cow's lifetime spent in early lactation and, thus, the occurrence of disease, metabolic disorder and reproduction failure associated with this period.***Although little is known about the biological control of persistency, factors such as milking frequency, completeness of milk removal, parity, photoperiod, nutrient intake and gestation have been shown to affect it. Recent work carried out in my laboratory, have demonstrated that the hormone prolactin (PRL), contrary to what was believed, is galactopoietic in dairy ruminants. If basal level of PRL was not clearly associated with level of milk production, the milking-induced PRL release was correlated to level of milk production Anti-apoptotic effects of PRL have been reported in the mammary gland of rodents and, accordingly, we found more apoptosis in the glands of cows where PRL secretion was inhibited. Therefore, it is possible that PRL, especially the milking-induced PRL, is an important factor for lactation persistency by limiting the loss of cells and maintaining cell differentiation. However, we also found that the galactopoietic action of PRL is modulated at the level of the mammary gland by a mechanism that remains to be elucidated. ******My hypotheses are:***-The milking-induced release of hormone is important to maintain the differentiation, the secretory activity and the survival of the mammary epithelial cells.***- Several factors affect milk production and lactation persistency by modulating the amount of hormones release at milking and/or mammary gland responsiveness to them.******My short range objectives are:***1- To determine the factors controling the magnitude of milking-induced release of PRL***2- To determine the mechanisms by which local factors affect lactation persistency.***3- To determine the mechanism(s) by which systemic factors affect lactation persistency