Early histological studies revealed that when animals become vitamin A deficient, proper differentiation is not maintained in various epithelial tissues (1). The trachea, for instance, undergoes squamous metaplasia resulting in keratinized epithelium whereas the testicular seminiferous tubules of vitamin A-deficient animals do not undergo keratinization and become severely atrophic (1). However, when retinol (vitamin A alcohol) is provided to the animal, tissue repair is permitted and improperly differentiated cells are rapidly replaced by normal cells (2). These observations indicate that vitamin A plays an essential role in cellular differentiation, and that the effects of vitamin A are tissue-specific. Furthermore, it is a common experience that in some organs, such as liver, no striking morphological changes occur in vitamin A deficiency (1). In one isolated report, the liver of germfree vitamin A-deficient rats was described to be necrotic (3). As it was customary in the past to use morphological criteria to determine whether a certain organ is a "target" organ, i.e., was in "need" for retinol, the liver is still not commonly considered as the target organ for retinol. Such conclusion is in contrast to biochemical evidence which suggests that the liver is a target for retinol (4,5).
The discovery of two novel intracellular vitamin A binding proteins has restored the role of the liver in vitamin A dependency. I will describe the characteristics of these proteins and discuss their possible role in the liver. To understand the possible function of these proteins, information concerning the metabolism of compounds with vitamin A activity will also be presented.
RETINOL AND RETINOIC ACID
From the family of compounds with vitamin A activity, now called "retinoids" in analogy with steroids (6), retinol (vitamin A alcohol) is the most active. Retinol supplied by the diet as esters or in the form of carotenoids covers all physiological functions; however, retinoic acid (vitamin A acid), the oxidative product of retinol in vivo