Acid-labile subunit regulation during the early stages of liver regeneration: implications for glucoregulation

The initiation of liver regeneration is regulated by endogenously produced growth factors and cytokines and is accompanied by suppression of growth ho rmone (GH) binding to hepatocytes. We have demonstrated some of these facto rs, particularly GH, which modulate acidlabile subunit (ALS) expression in vitro. Consequently, we investigated ALS hepatic mRNA and serum levels in r ats for 24 h after partial hepatectomy (PHx). There was a significant suppr ession of ALS gene expression (similar to 50%, P < 0.005) and serum levels (<similar to>30%, P < 0.02) by 12 h in PHx rats relative to controls. Relat ive to intact animals, hepatic mRNA and serum levels of ALS were suppressed by <similar to>60% at 24 h. Similarly, hepatic GH receptor mRNA levels wer e significantly reduced in PHx animals. Moreover, hepatocytes isolated from PHx animals were less responsive to GH than those from controls. Overall, our results demonstrate that suppression of ALS gene expression and serum l evels during liver regeneration relates to lowered hepatic GH sensitivity. Suppressed circulating ALS may alter insulin-like growth factor bioavailabi lity and constitute a mechanism to maintain relatively normal glucoregulati on after loss of liver mass.