The objective of the proposed nutritional and biochemical research is to continue to define molecular mechanism(s) of action of micronutrient vitamin A (retinol) and its metabolite retinoic acid in developing organs other than the eye. Retinol and retinoic acid interactions with the genome will be studied during perinatal development of lungs, liver, and testes. Changes which occur in the gene expression during retinol deficiency will be studied in the whole animal made retinol deficient by dietary restriction and shortly after refeeding with retinol or retinoic acid (refeeding model). In the analysis of interaction of this nutrient with the genome, two specific intracellular binding proteins for retinol (CRABP) and for retinoic acid (CRABP) will receive particular attention. Using the refeeding model, it will be explored whether and how the genes coding for these proteins are regulated by their respective ligands and by hormones. Furthermore, it will be studied how genes for these proteins are being regulated during perinatal development of various organs with special emphasis on the lung and testicular differentiation. The cells expressing genes for these binding proteins will be identified in pulmonary and testicular tissue. It will be attempted to clarify the tissue specific action of retinol and retinoic acid by studying proteins binding to the promoter regions of CRBP and CRABP genes. Finally, experiments are proposed to detect and characterize early genes activated by retinol and retinoic acid.
