SECRETION OF N-(4-HYDROXYPHENYL) RETINAMIDE-RETINOL-BINDING PROTEIN FROM LIVER PARENCHYMAL-CELLS - EVIDENCE FOR REDUCED AFFINITY OF THE COMPLEX FOR TRANSTHYRETIN

The synthetic retinoid 4-HPR has been shown to markedly lower the plas ma concentration of both retinol and REP in rats and humans. We have s tudied the effect of 4-HPR on the secretion of retinol-RBP from liver cells in vivo and in vitro. In rats maintained with a normal diet, a v itamin A-deficient diet or a normal diet supplemented with 4-HPR, chyl omicrons [H-3]retinyl esters were rapidly cleared from the plasma, The secretion of chylomicron-derived [H-3]retinol from tissues to the cir culation, however, was different, In control rats, the lymph-derived [ H-3]retinol peaked after about 2 hr, whereas 4-HPR treatment effective ly reduced this peak of [H-3]retinol, Our results suggest that 4-HPR i nhibits secretion of rerinol-RBP from the liver, Therefore, we decided to study the effect of 4-HPR on the secretion of REP using the human hepatoma cell line HepG2. Retinol and 4-HPR were found to induce the s ecretion of REP. The medium from cells treated with 4-HPR was immunopr ecipitated with antibodies against human REP. HPLC analysis of the pre cipitated REP revealed the presence of 4-HPR, When the medium from cel ls incubated with either 4-HPR or retinol was applied to a TTR affinit y column, we found that RBP from cells incubated with I-HPR had a cons iderably reduced affinity far TTR, We conclude that 4-HPR binds REP an d thereby induces secretion of REP in HepG2 cells, and that the secret ed 4-HPR-RBP complex has a reduced affinity for TTR, This observation may explain the 4-HPR-induced reduction of plasma retinol and REP obse rved in in vivo studies. (C) 1997 Wiley-Liss, Inc.