PLASMA DELIVERY OF RETINOIC ACID TO TISSUES IN THE RAT

All-trans-retinoic acid (RA) activates Ligand-dependent transcription factors that regulate retinoid-responsive gene expression. It is assum ed that all-trans-RA is formed within cells through in situ oxidation of retinol derived from the circulation. However, the circulation cont ains low level of all-trans-RA (approximately 0.2-0.7% of that of plas ma retinol). Our studies investigated the extent to which plasma all-t rans-RA contributes to tissue pools of this retinoid and explored fact ors responsible for regulating its uptake by tissues and cells. Rats w ere continuously infused, to steady state, with all-trans-[H-3]RA. Fro m measures of specific activities of all-trans [H-3]RA at steady state , we determined that the preponderance of all-trans-RA in brain and li ver was derived from the circulation. For six other tissues, approxima tely 10-30% of the retinoid was derived from the circulation, but panc reas and testis derived very little from the circulating pool. In othe r studies, we showed that retinoid nutritional status influences clear ance of a bolus dose of all-trans-RA and that neither the rate of cell ular all-trans-RA uptake nor its intracellular half-life is influenced by cellular lipid levels. Taken together, our data indicate that plas ma all-trans-RA contributes to tissue pools of this retinoid and that specific and physiologically responsive cellular processes mediate its uptake.