METABOLIC ADAPTATION AND CONTROL OF LACTATION IN HUMANS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在过去的二十年里，美国和西欧重新引起了人们对母乳喂养的兴趣和专业知识。母乳被普遍认为是婴儿的理想食物，母乳喂养对母亲、婴儿和他们之间的关系有实际和潜在的好处。在美国，大约50%的妇女选择母乳喂养婴儿，这对婴儿和母亲都有实际和潜在的好处。这些妇女中的一些人在尝试母乳喂养(乳汁不足综合症)时失败了，而另一些人则被认为是母乳喂养失败的高危人群(有些是早产儿和十几岁的母亲)。乳糖量的主要决定因素是乳糖产量。在之前的资助期间，我们已经演示了在24小时禁食后没有困难，与对照组相比，在底物或激素浓度方面没有差异。此外，我们还证明：1)人类乳房能够从头合成乳糖的葡萄糖和半乳糖部分(己酮合成)，2)与24小时禁食值相比，来自乳糖合成的乳糖从30%增加到近50%，3)血浆游离氨基酸库以外的氨基酸来源对乳蛋白合成有贡献，以及4)人类生长激素(RhGH)增加了人类乳汁的投射和肝脏的糖异生。最后，我们证明了乳脂小球含有足够的特定的信使核糖核酸，使得研究调节人类乳房中基因表达的底物和激素因素成为可能。拟议的研究建立在我们目前的知识和技术的基础上，以提供关于产妇对哺乳的适应和乳糖生产调节的深入信息。通过更好地了解调节乳糖生产的因素，我们将能够更好地为那些与成功母乳喂养作斗争的人设计腹间策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Over the last two decades, renewed interest and expertise in and about breatfeeding has occurred in the U.S. and Western Europe. Human milk is universally accepted as the ideal food for infants and breastfeeding has real and ptential benefits for the mother, the infant and to their relationship. In the United States about 50% of women choose to breastfeed their infants dcespite all of the real and potential advantages to both the infant and mother. A number of these women have been unseccessful, in their attempts to breastfeed (insufficient milk syndrome) and others are known to be at high risk of breatfeeding failure (somen with premature infants and teenage mothers). The primary determinant of milk volume is lactose production. Over the previous period of funding, we have demostrated that following a 24 hr fast without difficulty and have no differences in substrate or hormone concentrations whien compared to controls. In addition, we demonstrated: 1) the human breast was capable of de novo synthesis of both the glucose and galactose moieties of lactose (hexoneogenesis), 2) The fraction of lactose derived from hexoneogenesis increased from 30% to nearly 50% comparing the fed to the 24 hr fasted values, 3) a source of amino acids other than the plasma free amino acid pool contributes to milk protein synthesis, and 4) human groth hormone (rhGH) increases human milk projection and hepatic gluconeogenesis. Finally we demonstrated that milk fat globules contain sufficient specific mRNA to permit investigations of the substrate and hormonal factor that regulatze gene expression in the human lactating breast. The proposed studies build on our current knowledge and techniques to provide indepth information on the maternal adaptation to lactation and the regulation of lactose production. By better understanding the factors regulating lactose production we will be better able to design interventinal strategies for individuals who struggle with successful breast feeding.