The studies described in this application are designed to explore the processes which generate and maintain tissue and cellular levels of retinoic acid (vitamin A acid). The identification of retinoic acid as a natural morphogen and the description of nuclear receptors for retinoic acid have greatly expanded the interest in and the research activity directed towards understanding mechanistically how retinoic acid functions in regulating gene transcription. Little information, however, is currently available regarding the origin of the retinoic acid present in tissues or cells or the factors which regulate tissue and cellular retinoic acid levels. The studies proposed in this application will provide significant new information about the cellular and tissue processes which generate and maintain tissue levels of retinoic acid. Thus, these proposed studies will provide new information regarding processes which are essentially involved in the expression of vitamin A action. This proposal is divided into four Specific Aims. The studies proposed in Specific Aim 1 are designed to investigate the plasma turnover of retinoic acid and to assess the contribution that plasma retinoic acid makes to tissue retinoic acid pools in control chow fed male rats. Specific 2 proposes studies which will explore the effects of age and sex on whole body retinoic acid synthesis rates, plasma and tissue retinoic acid levels, and the contribution which plasma retinoic acid makes to tissue retinoic acid pools. The goal of Specific Aim 3 is to gain an understanding of how different states of retinoid (vitamin A) and carotenoid nutriture influence tissue and plasma levels of retinoic acid, whole body retinoic acid synthesis rates, and the metabolic origin (plasma vs. tissue synthesis) of the retinoic acid present in tissues.
Specific Aim 4 will examine and characterize the formation of retinoic acid in isolated rat testis Sertoli cell preparations and identify factors which are responsible for regulating retinoic acid levels in these cells.
