The hepatic synthesis of several
proteins, including both
albumin and
transferrin is increased in the
nephrotic syndrome. While active suppression of
albumin synthesis by
lymphokines has been described, it has been assumed that augmentation of
albumin synthesis is governed by a physical factor, plasma oncotic pressure (pi), and that this regulation is by a direct effect of pi on hepatocytes. The mechanisms have not been defined. Furthermore, experiments relying on suppression of
protein synthesis may only test non-specific inhibitory effects of the experimental 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 with passive
Heymann nephritis (HN), a model of the
nephrotic syndrome. Synthesis (incorporation of [35S]
methionine) into both
albumin and
transferrin was increased significantly. The stimulatory effect of these sera was not extinguished by addition of rat or
human albumin to the medium prior to or during incubation, even when pi in the incubation medium was increased to normal plasma levels by added
albumin. Incorporation of [35S]
methionine into
albumin was 7841 +/- 394 cpm/mg cell
protein 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 presence of control serum and in the absence of added
albumin (medium pi 2.06 +/- 0.26 mm Hg, P < 0.001). The stimulatory activity was preserved following heating of serum for one hour at 60 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)