Pretranslational regulation of albumin synthesis in tumor-bearing mice. The role of anorexia and undernutrition

Abstract

Hepatic albumin synthesis, serum albumin turnover, and hepatic albumin messenger RNA (mRNA) content were evaluated in mice bearing a transplantable low differentiated tumor (MCG 101). Results obtained on tumor-bearing mice were compared with results obtained from non-tumor-bearing animals that were either freely fed, food restricted so that their body composition was similar to tumor-bearing animals (pair-weighed), fed a protein-free diet for 5 days, or fasted for 48 hours. Tumor-bearing animals became hypoalbuminemic (33 +/- 5 vs. 44 +/- 3 g/L in freely fed mice), which could be explained by both depressed albumin synthesis (1.95% +/- 0.20% vs. 2.67% +/- 0.27%/h in freely fed mice) and increased albumin degradation. Pair-weighed and protein-calorie malnourished controls had reductions in albumin synthesis (1.81% +/- 0.18% and 1.67% +/- 0.17%/h, respectively) similar to tumor-bearing animals, and the starved controls had the lowest synthetic rates (1.07% +/- 0.10%/h). Albumin degradation was increased only in tumor-bearing animals. Hepatic albumin mRNA in undernourished animals was less (tumor bearing, 32% +/- 5%; pair weighed, 47% +/- 4%; 48 hours fasted, 18% +/- 2%; and protein-calorie malnourished, 26% +/- 3%) than 50% of the mRNA content in the livers of freely fed control mice. Messenger RNA-directed synthesis of albumin in vitro was also depressed to a variable degree in tumor-bearing and malnourished non-tumor-bearing controls. The hypoalbuminemia in tumor-bearing animals could not be prevented by daily injections of a prostaglandin synthesis inhibitor (indomethacin, 1 microgram/g body wt), but the hepatic acute phase protein serum amyloid P decreased from 157 +/- 12 to 103 +/- 9 micrograms/mL in indomethacin-treated tumor-bearing mice (P less than 0.01). It is concluded that increased albumin degradation seen in tumor-bearing animals cannot be explained by associated malnutrition, whereas tumor-associated malnutrition can explain to a large extent the depressed albumin synthesis. Decreased albumin synthesis in tumor-bearing animals correlated in part with a decreased quantity of liver albumin mRNA. The results of the current study are consistent with either a reduced transcription of the albumin gene or a change in albumin mRNA processing and stability communicated by anorexia and malnutrition.