HORMONAL REGULATION OF GENE EXPRESSION DURING LACTATION IN HUMANS

点击翻译按钮获取中文摘要

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. ABSTRACT 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 infnants and breastfeeding has real and potential benefits for the 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 specifc mRNA to permit investigations of the substrate and hormonal factors that regulate gene expression in the 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. HYPOTHESIS The Hypothesis to be tested is that rhGH will increase the expression of the gene for alpha-lactalbumin and GLUT 1 and 3 but not PEPCK following 4 days of treatment at a dose of 0.1 mg/kg-day. SPECIFIC AIMS To determine whether rhGH acutely increases the expression of a-lactalbumin in human mammary tissue.