Role of Retinol in RBP Secretion

Extensive studies conducted during the past decade have demonstrated that the availability of retinol to the liver cell plays a critical role in the control of RBP secretion from the cell. The effects of retinol depletion and of retinol repletion are illustrated in Fig. 4. In the retinol-deficient state, the secretion of RBP from the liver is blocked, resulting in the accumulation of an enlarged pool of apo-RBP in the liver, and a concomitant decline in serum RBP level (Muto et al., 1972 J. E. Smith et al., 1973a). Conversely, repletion of retinol-deficient rats with retinol stimulates the rapid secretion of RBP from the expanded liver pool into the plasma. 

These data indicated that the increased level of RBP in serum after retinol injection mainly represented the release of RBP from an existing pool in the liver, rather than newly synthesized protein. Similarly, it was observed (Peterson et al., 1973) that actinomycin D did not block the retinol-stimulated mobilization of RBP from the livers of vitamin A-deficient rats. 

Repletion of retinol-deficient rats can also be effectively achieved by the intravenous injection of retinol dispersed in a 20% Tween 40 solution (Smith et al., 1980 Fig. 4). Such an injection produces a rapid, dose-related increase in the serum concentration of RBP. The changes in serum RBP levels seen after the injection of retinol in a 20% Tween 40 solution closely resembled those previously seen after the injection of vitamin A (retinyl esters) in association with lymph chylomicrons. However, the amount of retinol required to stimulate the secretion of a given amount of RBP from the liver was about two to three times that required when retinol (retinyl esters) was injected in chylomicrons. As discussed by Smith et al. (1980), this quantitative difference is probably due to differences in the tissue distribution pattern of retinol when injected in the Tween 40 solution, compared to its administration in the form of chylomicrons. 

The block in RBP secretion seen after retinol depletion is highly specific for RBP. Thus, neither retinol depletion and deficiency nor retinol repletion of 

A study was conducted to explore the role of retinol in the control of the rate of synthesis of RBP in the liver (Soprano et al., 1982a). In this study, normal rats were compared with retinol-depleted rats and with retinol-depleted rats that had been acutely repleted intravenously with retinol. Both the in vivo relative rate of RBP synthesis and the in vitro translatable level of RBP-specific messenger RNA (mRNA) were measured. Both the relative rate of RBP synthesis (approximately 0.26%) and the translatable level of RBP-specific mRNA (approximately 0.14%) were found to be constant regardless of the retinol status of the rats. These results indicate that retinol, the molecule that RBP specifically binds and transports, does not appear to control the rate of synthesis of RBP or the translatable level of RBP-specific mRNA in the liver of the rat. RBP thus appears to be unusual since the synthesis of other binding proteins for which information is available is, in general, controlled by their specific ligands (see Soprano et al., 1982a, for references). This study further demonstrates that control of the rate of RBP secretion and of plasma RBP levels by retinol must be exercised fully at a locus beyond that of RBP synthesis. 

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