Uptake and cellular transport of [11-3H] all-trans-retinoic acid in the liver of vitamin A-deficient hamsters

In this study, we examined, by ultrastructural autoradiography, the uptake and intracellular transport of 3H]all-trans-retinoic acid (3H]RA) in the livers of vitamin A-deficient hamsters. Four-week-old animals were administered 25 microCi of 3H]RA by gavage, and, at different intervals thereafter, one animal was sacrificed. Their livers were excised and processed for autoradiography. Radioactive grains were observed to pass randomly through the plasma membrane by diffusion. No evidence of retinoid internalization by endocytosis was observed. Between 1 and 30 min after gavage, the radioactivity in parenchymal cells was associated mainly with rough endoplasmic reticulum (RER) and mitochondria. The labeling over nuclei was apparent at 1 min, remained relatively high up to 30 min, and subsequently decreased. At 2 and 5 hr, only a few grains were observed over nuclei, RER and mitochondria. At 24 hr, most of the labeling was associated with endothelial cells and sinusoidal spaces, indicating mobilization of 3H]RA from the liver. The results indicate that 3H]RA is transported through the plasma membrane by transmembrane diffusion without endocytosis and, after entering the cells, the ligand is rapidly translocated into nuclei.