Regulation of asialoglycoprotein receptor expression in rat hepatocytes cultured under proliferative conditions

The expression of many glycoproteins on the surface of hepatocytes has been related to the state of differentiation of the liver. In particular, the asialoglycoprotein receptor (ASGP-R) is modulated in many physiological and pathological conditions in which hepatocyte proliferative activity is modified. We studied ASGP-R expression in primary monolayer cultures of rat hepatocytes stimulated to proliferate by the addition of epidermal growth factor and insulin. In proliferating hepatocytes the receptor concentration on the cell surface was lowered, with no modifications in its distribution; similarly, both the binding activity and the amount of specific transcripts were decreased. The decreases were related to the peak of cellular growth, as judged by [3H]thymidine incorporation into DNA. The results suggest the presence of a cell cycle-dependent ASGP-R expression also in in vitro systems; this control could be exerted by a decreased availability of receptor-specific mRNA molecules or on the stability of transcripts.