9-CIS-RETINOYL-BETA-D-GLUCURONIDE IS A MAJOR METABOLITE OF 9-CIS-RETINOIC ACID

The in vivo metabolism of 9-cis-retinoic acid (9-c-RA), an endogenous ligand of retinoid X receptors (RXRs), which can also bind to retinoic acid receptors (RARs), was examined in pregnant mice and rats followi ng a single oral dose of 100 mg 9-cis-retinaldehyde (9-c-RAL) / kg bod y weight. 9-Cis-retinoyl-beta-D-glucuronide (9-c-RAG), a metabolite no t found in vivo before, was a major metabolite of 9-c-RA in mouse plas ma and was also present in all mouse tissues examined as well as in ra t plasma. In both species putative oxidation products of retinoic acid s and high levels of retinyl esters were found. Concentrations of reti noic acid isomers and retinoyl-beta-D-glucuronides in the mouse plasma greatly exceeded those of the rat plasma. The finding of high levels of 9-c-RAG underlines the importance of glucuronidation in the metabol ism of retinoids.