Regulation of beta-adrenergic receptor expression in rat liver

To begin defining the factors regulating neurotransmitter receptor expression, we examined beta-adrenergic receptors in rat liver in vivo and in primary liver cultures under defined hormonal conditions. beta-receptors described a remarkable developmental profile in vivo, increasing fivefold between embryonic days 16 and 20, and decreasing tenfold by early adulthood. The developmental decrease reflected reduced receptor number without a change in receptor properties. The ontogenetic decrease appeared to be specific for beta-receptors; alpha-receptors developed in a hyperbolic fashion, reaching high plateau values by the third postnatal week. Adult rat liver cells plated into culture re-expressed high beta-receptor levels, exhibiting a 4-8-fold increase. A similar pattern of expression of the beta-receptors, having similar pharmacological properties, was observed in primary liver cultures maintained in serum-free medium, in a serum-supplemented medium or in several variations of a serum-free, hormonally defined medium designed for primary liver cultures. Thus, the degree of expression of the beta-receptors was not found affected by various hormones, by serum, or by any medium condition. By contrast, the degree of expression of the beta-receptors was markedly sensitive to cell density. High expression of the beta-receptors was observed at low cell densities (1-3 x 10(6) cells/150 mm dish), and low expression or no expression was observed in confluent cultures (10-20 x 10(6) cells/150 mm dish). Our experiments suggest that beta-receptor expression does not follow an immutable program, but may be regulated by density-dependent cell-cell interactions.