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 breastfeeding 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 potential benefits for the mother, the infant and to their relationship. In the United States about 50% of women choose to breastfeed their infants despite all of the real and potential advantages to both the infant and mother. A number of these women have been unsuccessful in their attempts to breastfeed (insufficient milk syndrome) and others are known to be at high risk of breastfeeding failure (women with premature infants and teenage mothers). The primary determinant of milk volume is lactose production. We have previously demonstrated that following a 24 hr fast, lactating women have a 35% higher rate of glucose turnover than controls, tolerate a 24 hr fast without difficulty and have no differences in substrate or hormone concentrations when 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 growth hormone (rhGH) increases human milk production and hepatic gluconeogenesis. Finally we demonstrated that milk fat globules contain sufficient specific mRNA to permit investigations of the substrate and hormonal factors that regulate gene expression in the human lactating breast. Understanding whether and how the mRNA in the milk fat globules are regulated is the initial focus of these studies. Because of our previous experience with rhGH, we will initially test the acute effect of rhGH on alpha lactalbumen mRNA expression in milk fat globules. Over all, research program will 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 interventional strategies for individuals who struggle with successful breast feeding.
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