Vol. 280, Issue 2, E287-E295, February 2001
Acid-labile subunit regulation during the early stages of
liver regeneration: implications for glucoregulation
Patric J. D.
Delhanty,
Carolyn D.
Scott,
Sunita
Babu, and
Robert
C.
Baxter
Department of Molecular Medicine, University of Sydney, Kolling
Institute of Medical Research, St. Leonards, New South Wales 2065, Australia
The initiation
of liver regeneration is regulated by endogenously produced growth
factors and cytokines and is accompanied by suppression of growth
hormone (GH) binding to hepatocytes. We have demonstrated some of these
factors, particularly GH, which modulate acid-labile subunit (ALS)
expression in vitro. Consequently, we investigated ALS hepatic mRNA and
serum levels in rats for 24 h after partial hepatectomy (PHx).
There was a significant suppression of ALS gene expression (~50%,
P < 0.005) and serum levels (~30%,
P < 0.02) by 12 h in PHx rats relative to
controls. Relative to intact animals, hepatic mRNA and serum levels of
ALS were suppressed by ~60% at 24 h. Similarly, hepatic GH
receptor mRNA levels were 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 levels during liver
regeneration relates to lowered hepatic GH sensitivity. Suppressed
circulating ALS may alter insulin-like growth factor bioavailability
and constitute a mechanism to maintain relatively normal
glucoregulation after loss of liver mass.
insulin-like growth factor; growth hormone receptor; hepatocyte
