METABOLIC ADAPTATION AND CONTROL OF LACTATION IN HUMANS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在过去的二十年里，美国和西欧对母乳喂养重新产生了兴趣和专业知识。母乳被普遍认为是婴儿的理想食物，母乳喂养对母亲、婴儿和他们的关系都有真实的和潜在的好处。在美国，大约50%的妇女选择母乳喂养她们的婴儿，因为母乳喂养对婴儿和母亲都有真实的和潜在的好处。其中一些妇女在尝试母乳喂养时没有安全感（乳汁不足综合症），另一些妇女则有母乳喂养失败的高风险（有早产儿和未成年母亲的妇女）。乳量的主要决定因素是乳糖产量。在之前的资助期间，我们已经证明，与对照组相比，24小时禁食后没有困难，底物或激素浓度没有差异。此外，我们还证明了：1）人乳房能够从头合成乳糖的葡萄糖和半乳糖部分（己酮生成），2）与进食与24小时禁食值相比，源自己酮生成的乳糖的分数从30%增加到接近50%，3）除血浆游离氨基酸库之外的氨基酸源有助于乳蛋白合成，4）人生长激素（rhGH）增加母乳分泌和肝脏新生。最后，我们证明，乳脂球含有足够的特定mRNA，允许调查的底物和激素因子，调节人类哺乳期乳房的基因表达。拟议的研究建立在我们现有的知识和技术，提供深入的信息，产妇适应哺乳和乳糖生产的调节。通过更好地了解调节乳糖产生的因素，我们将能够更好地为那些难以成功母乳喂养的人设计干预策略。

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.