Retinol-binding protein secretion from the liver of N-(4-hydroxyphenyl) retinamide-treated rats

N-(4-Hydroxyphenyl)retinamide (HPR; Fenretinide), a synthetic retinoid possessing antitumor activity, depresses plasma retinol and retinol-binding protein (REP) concentrations. In study 1, the ability of retinol or HPR to induce REP secretion from the livers of vitamin A-deficient rats was compared. A large apoRBP pool accumulated in the liver rough microsomes of these rats. Following retinol repletion, 80% of the accumulated REP was rapidly secreted into the plasma. In contrast, HPR treatment only induced two-thirds of the REP secretion observed with retinol. Prior colchicine treatment caused a large REP accumulation in the Golgi-enriched fraction following retinol repletion. HPR plus colchicine treatment produced significantly less accumulation of REP in the Golgi-enriched fraction than did retinol. In study 2, HPR treatment of vitamin A-adequate rats caused REP to accumulate in the liver rough microsomes. When vitamin A-adequate rats were treated with colchicine, the concentration of REP in the Golgi-enriched fraction increased 2.9-fold. However, significantly less REP accumulated in the Golgi following HPR treatment. These studies demonstrate that HPR will induce liver REP secretion, but to a lesser degree than retinol. Further more REP remained in the rough microsomes of HPR treated, vitamin A-adequate rats, indicating that HPR depressed the amount of REP secreted.