Nutritional regulation of endoplasmic reticulum biogenesis in mammary epithelial cells

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There are 945,000 dairy cows in Canada on 10,951 farms and they produce all the fluid milk consumed domestically. The cows' diets are formulated by highly qualified nutritionists employed by feed companies or as independent consultants. One of the goals of ration formulation for dairy cows is to maximize the efficiency of dietary protein capture in milk. Cows typically consume over 4 kg/d of crude protein and secrete approximately 25% of that into milk. The 75% of protein intake that is not captured in milk is excreted as nitrogenous compounds in manure and represents both an environmental and financial loss. Protein capture efficiencies of up to 45% are possible but our understanding of how to consistently obtain such high efficiency is inadequate. The long-term goal of my research program is to improve understanding of the control of milk protein yield in the mammary glands of dairy cows so that responses to dietary manipulation can be predicted quantitatively. We have previously found that milk protein yields cannot be predicted from knowing the concentrations of amino acids in blood. Within minutes of exposure to hormonal and nutritional stimuli, mammary cells up-regulate their rate of mRNA translation into protein. Over several days of nutritional intervention, it appears that factors that control expansion of the intracellular machinery for milk protein secretion during mammary cell differentiation become important regulators of milk protein yield. The main component of this machinery is an organelle called the endoplasmic reticulum (ER). Because ER biogenesis is a new area for investigation, we propose to develop methods to assay ER size and secretory capacity of mammary cells. Once developed, we will use the methods to explore connections between translation activation and secretory differentiation, and to explore effects of growth factors and nutrients on mammary ER biogenesis. While ER biogenesis may be an important contributor to changes in active milk secretory cell numbers, it is not the only contributor, so we will develop a computer simulation model of mammary cell turnover that includes proliferation and apoptosis in addition to differentiation in order to robustly test our hypotheses and identify gaps in knowledge. Findings will be used to design research to improve efficiency of milk protein production. Efficient production is desirable because the protein of milk supplies an ideal amino acid profile for infant growth. In addition, bioactive peptides derived from fermentation or digestion of milk proteins possess functional value in treatment and prevention of symptoms of the human metabolic syndrome including obesity, atherogenesis, arterial hypertension, and type 2 diabetes.