New aspects in vitamin A metabolism: The role of retinyl esters as systemic and local sources for retinol in mucous epithelia

Vitamin A and its active metabolites are important for growth and differentiation of a variety of cells, mainly in mucosa-associated epithelia, where they exhibit a wide spectrum of activities. Vitamin A, stored as retinyl esters (REs), is delivered from liver stores into the bloodstream as retinol bound to retinol binding protein. This process is regulated homeostatically, ending up in a more or less constant plasma retinol level. In situations of a high vitamin A demand (e.g., inflammation, diseases, prenatal period), this supply can be insufficient because of delayed production of retinol binding protein, leading to local deficiencies and impairment of structure and function in the respective tissues. This delay may be overcome by cellular RE stores. Several cell types, including buccal mucosa cells, can take up RE. Retinyl palmitate is taken up when it is applied topically to either metaplastically mutated rat vaginal epithelium (as a gel) or to human meta- and dysplastic bronchial epithelia (via inhalation) that have a vitamin A deficiency. In rats and humans, the modified epithelia can be normalized, at least in part. In conclusion, topically applied retinyl esters may be a promising therapy for local retinol deficiencies and may reverse the morphological alterations of the epithelium in tissues that are vitamin A deficient.