The Effects of Chylomicron Vitamin A on the Metabolism of Retinol-binding Protein in the Rat

Vitamin A-deficient rats have low levels of retinol-binding protein (RBP) in serum and elevated levels of RBP in their livers. Chylomicrons containing newly absorbed vitamin A were injected intravenously into vitamin A-deficient rats, and the levels of vitamin A and of RBP in serum were determined on samples collected serially from individual rats. Data were also obtained on liver immunoreactive RBP concentrations with samples obtained at death. Chylomicrons were used so that the vitamin could be administered physiologically, in the form in which it is normally absorbed. After the injection of chylomicrons containing vitamin A a rapid increase in the serum levels of RBP and of vitamin A occurred, with maximal levels observed at 2 to 4 hours. The magnitude of the response was directly related to the amount of vitamin A given, in the dose range 0 to 17 µg of vitamin A. In an initial study of the dose range of 0 to 32 µg, a maximal response was obtained with doses of 16 µg or greater. Substantial increases in serum RBP levels were observed soon after chylomicron clearance, by 45 min after chylomicron injection. Livers were obtained 2 hours after chylomicron injection in rats given graded amounts of vitamin A. The dose-response relationship of the increase in serum RBP was mirrored by a complementary dose-related decrease in the level of RBP in the liver. Release of RBP from liver into serum, which was a function of the amount of vitamin A given, apparently occurred. Rats pretreated with either puromycin or cycloheximide also showed a rapid and substantial rise in serum RBP and vitamin A levels, after the injection of vitamin A. The results indicate that the increased level of RBP in serum after vitamin A injection mainly represents the release of previously formed RBP from an existing pool in the liver, rather than representing newly synthesized protein. The secretion of RBP by the liver is regulated efficiently by the availability of vitamin A for the formation of the retinol-RBP complex.