METABOLIC ADAPTATION AND CONTROL OF LACTATION IN HUMANS

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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.