ALBUMIN AND TRANSFERRIN SYNTHESIS ARE INCREASED IN H4 CELLS BY SERUM FROM ANALBUMINEMIC OR NEPHROTIC RATS

The hepatic synthesis of several proteins, including both albumin and transferrin is increased in the nephrotic syndrome. While active suppr ession of albumin synthesis by lymphokines has been described, it has been assumed that augmentation of albumin synthesis is governed by a p hysical factor, plasma oncotic pressure (pi), and that this regulation is by a direct effect of pi on hepatocytes. The mechanisms have not b een defined. Furthermore, experiments relying on suppression of protei n synthesis may only test non-specific inhibitory effects of the exper imental intervention. We tested an alternative hypothesis that a serum factor(s) present in hypooncotic states stimulates albumin synthesis. We incubated an immortalized cell line derived from rat hepatocytes ( H4 cells) with serum from Nagase analbuminemic rats (NAR) and rats wit h passive Heymann nephritis (HN), a model of the nephrotic syndrome. S ynthesis (incorporation of (35)methionine) into both albumin and tra nsferrin was increased significantly. The stimulatory effect of these sera was not extinguished by addition of rat or human albumin to the m edium prior to or during incubation, even when a in the incubation med ium was increased to normal plasma levels by added albumin. Incorporat ion of S-35methionine into albumin was 7841 +/- 394 cpm/mg cell prot ein using 10% NAR serum in the presence of human albumin (medium pi 26 .1 +/- 0.17) versus 5149 +/- 420 cpm incorporation (P < 0.05) in the p resence of control serum and in the absence of added albumin (medium p i 2.06 +/- 0.26 mm Hg, P < 0.001). The stimulatory activity was preser ved following heating of serum for one hour at 60 degrees C. These obs ervations suggest that albumin and transferrin synthesis is stimulated by a heat stable factor found in serum when plasma pi is reduced, rat her than as a consequence of the interaction of pi directly with the h epatocyte.