Vitamin A intake and in vivo expression of the genes involved in retinol transport.

Two different metabolic alterations in vitamin A status are known to cause changes in the amount of circulating retinol-binding protein (RBP) and cellular retinol-binding protein (CRBP) in experimental animals; namely vitamin A deficiency, characterized by depleted retinol-liver stores and hypervitaminosis A, characterized by hepatic accumulation of retinyl esters. We have induced vitamin A deficiency and hypervitaminosis A in two groups of rats with the aim of determining whether the expression of the genes coding for these two proteins might be directly regulated by retinol. Using human RBP and CRBP cDNAs as probes, we measured the rate of transcription of the two genes in liver nuclei from control and treated rats by run-on transcription assays, and the steady-state level of the mRNAs by Northern blot analysis of total liver RNA. The distribution profile of RBP and CRBP mRNAs on fractionated liver polysomes was also examined. We have found a threefold decrease in the hepatic level of CRBP mRNA in vitamin-A-deficient animals, while the RBP mRNA is not affected by this nutritional deprivation. The decreases does not correspond to a lower transcription rate of the gene and therefore it is likely to result from lower stability of the CRBP mRNA. In hypervitaminosis A, we do not observe any differences in both the steady-state level of the mRNAs and in the rate of transcription of the two genes. The results are discussed in terms of retinol-dependent stabilization of the mRNA coding for CRBP.