ABSTRACT
For more than 75 years, it has been known that vitamin A is critically important for growth and differentiation of epithelial cells, and it was soon realized that β-carotene is a provitamin that can replace vitamin A in the diet (1). As early as 1925, Wolbach and Howe (2) showed that vitamin A deficiency in rats led to the replacement of differentiated mature epithelium with squamous, keratinizing epithelial cells: Hyperkeratosis was observed in the skin, while hyperplastic and metaplastic changes were observed in epithelia of mucous membranes in vitamin A deficient rats. They concluded that vitamin A influenced the differentiation of epithelial cells, from the normal, simple, and pseudostratified phenotype to squamous, metaplastic lesions that start focally and spread throughout the epithelium. Shortly after, Nicholls (3) described phrynoderma, a distinct form of follicular hyperkeratosis, in African prisoners who also had night blindness and xerophthalmia (4). When treated with vitamin A containing cod live oil, both skin lesions and night blindness improved. In 1953, Fell and Mellanby (5) reported that the phenotype of chick epidermis in organ culture could be changed from keratinized to mucus-producing tissue by treatment with retinol or retinyl acetate. These
observations were followed by numerous studies focusing on the pharmacological action of retinoids and carotenoids in skin. This has ultimately resulted in the development of some thousand new synthetic compounds and the establishment of retinoids and carotenoids as treatment for various skin diseases (6-11). During the last years, the ability of retinoids to affect the gene expression and differentiation of epithelial cells in vivo and in vitro has been studied in great detail.
