Regulation of Retinol-Binding Protein Metabolism by Glucocorticoid Hormones in Cultured H4II EC3 Liver Cells*

Abstract

Studies were conducted to explore the effects of glucocorticoid hormones on the regulation of the metabolism of retinol-binding protein (RBP) by H4II EC4 rat hepatoma cells in culture. Cortisol, corticosterone, and the synthetic glucocorticoid analog dexamethasone all induced a 2- to 3-fold increase in accumulation of RBP. Half-maximal stimulation occurred at concentrations of dexamethasone in the range of 1-5 nM. Progesterone in the concentration range of 1-10 microM, inhibited the stimulatory effect of dexamethasone. Progesterone alone in this concentration range had no effect on RBP metabolism. By analogy with the studies of others, these observations with progesterone suggest that glucocorticoid receptors are involved in the effect of dexamethasone on RBP. As previously reported, RBP accumulated in the hepatoma cells when they were incubated in a medium free of serum and of vitamin A. The addition of retinol over a range from 3.5 nM to 3.5 microM stimulated a dose-dependent secretion of RBP from the cells into the medium. In longer experiments, retinol also stimulated the accumulation of RBP. Neither dexamethasone nor retinol had an effect on the accumulation or the cell to medium distribution of rat serum albumin or prealbumin at concentrations which were maximally stimulatory for RBP. When studied over a wide range of concentrations, retinol and dexamethasone incubated together produced approximately additive increases in the accumulation of RBP. Dexamethasone, moreover, did not affect the retinol-induced secretion of RBP. Thus, retinol and dexamethasone appear to function via different and independent mechanisms to regulate the metabolism of RBP by the liver cell.