Abstract
Abstract 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.
Highlights
Study I-The first study was designed to determine whether the injection of chylomicrons containing vitamin A would result in a rise in the level of serum retinol-binding protein (RBP), and if so to obtain information about the time course of the response and about its relationship to the amount of vitamin A injected
Within 1 hour after the injection of chylomicrons containing vitamin A, the serum RBP levels of the deficient rats rose to concentrations similar to those usually observed in control rats (1)
Maximal levels of serum RBP (60 to 70 pg per ml) at 1 hour after chylomicron injection were obtained with doses of 16 /.rg or greater of vitamin A
Summary
Vi’itarnin il-dejcient Rats-Fifty-two male weanling rats of the Holtzman strain were fed a vitamin A-free diet to deplete their vitamin A stores as described previously (1). The first (Study I) employed 12 rats, chosen at random, which had been fed the deficient diet for 36 days. These rats had a mean body weight of 237 g. We have previously observed that retinoic acid-supplemented rats are indistinguishable from unsupplemented vitamin h-deficient rats with regard to RBP levels in serum and liver and with regard to the response of serum RBP to oral vitamin A (1). Retinoic acid supplementation was discontinued 5 days before the second experiment (Study II) was carried out. Study II was conducted 26 days after Study I; at this time the rats weighed approximately 290 g each
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