Although it is known that maternal milk is important in increasing the neonate's reserves of vitamin A, many aspects of vitamin A delivery to, and metabolism in, mammary glands have not yet been studied. Here we investigate the hypothesis that the increased uptake of chylomicron triglyceride fatty acids by lactating mammary glands is associated with an increased input of vitamin A. The relationships among dietary vitamin A (and thus chylomicron vitamin A) and mammary gland vitamin A content, uptake and turnover, will be investigated in female rats. First we will test the hypothesis that delivery of vitamin A to, and retention by, mammary glands during late pregnancy and lactation is proportional to dietary vitamin A intake (AIM #1). Next we will test the hypothesis that chylomicrons (rather than plasma retinol-binding protein) are responsible for the diet-dependent enhancement in vitamin A uptake by mammary glands during lactation (AIM #2). Kinetic methods and model-based compartmental analysis will be used to determine the contribution of these two vehicles to uptake of vitamin A by mammary glands and transfer to milk at two levels of dietary vitamin A in lactating rats. We will also determine the chemical distribution and turnover of mammary tissue retinoids. Finally we will test the hypothesis that turnover of vitamin A from mammary glands is slow enough that lactation is associated with the potential for long-term accumulation of mammary gland vitamin A (AIM #3). In addition to contributing to our long-term goal of defining the dynamics of vitamin A metabolism in different nutritional, physiological and pathological states, results from these experiments have implications for maternal and child health, and for targeting other lipophilic anticancer agents [e.g., beta-carotene or the synthetic retinoid, N-(4-hydroxyphenyl)retinamide] to specific tissues.
