Metabolism of a physiological amount of all-trans-retinol in the vitamin A-deficient rat

Because only retinol and not all-trans-retinoic acid (atRA) can satisfy all of the functions of vitamin A, we have investigated the retinol metabolite s in tissues of vitamin A-deficient (VAD) rats responding to a radioactive dose of [20-H-3]all-trans-retinol. As expected, atRA is the major vitamin A metabolite present in the target tissues of VAD rats given a physiological dose (I mug) of [20-H-3]all-trans-retinol (atROL). Both atROL and atRA wer e detected by high-performance liquid chromatographic (HPLC) analysis of th e radioactivity extracted from the liver, kidney, small intestine, lung, sp leen, bone, skin, or testis of these animals. Novel retinol metabolites wer e observed in the aqueous extracts from the testis, lung, and skin. However , these metabolites were detected in very small amounts and were not charac terized further. Importantly, neither 9-cis-retinoic acid (9cRA), 9-cis-ret inol (9cROL), nor 13-cis-retinoic acid (13cRA) was present in detectable am ounts. The amounts of atRA varied in each tissue, ranging from 0.29 +/- 0.0 5 fmol of RA/g of tissue in the femurs to 12.9 +/- 4.3 fmol of RA/g of tiss ue in the kidneys. The absence of 9cRA in vivo was not due to degradation o f this retinoid during the extraction procedure or HPLC analysis of the ext racted radioactivity. As atROL completely fulfills all of the physiological roles of vitamin A, and 9cRA is not detected in any of the tissues analyze d, these results suggest that 9cRA may have no physiological relevance in t he rat. (C) 2001 Academic Press.