Effects of Partial Hepatectomy on Hepatic Insulinlike Growth Factor Binding Protein–1 Expression

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Abstract
Insulinlike growth factor binding proteins modulate the action of the insulinlike growth factors in various bioassays and may regulate the bioavailability of the insulinlike growth factors in vivo. Because the insulinlike growth factors may influence hepatic regeneration, we have examined the effect of partial hepatectomy on serum insulinlike growth factor binding proteins and on the abundance of insulinlike growth factor binding protein–1 messenger RNA in the liver. All rats were fasted before and after partial hepatectomy or sham operation to avoid the confounding effects of difference in food intake. Using a conventional protocol, 70% of the liver was removed, and groups of four or five rats were killed at different intervals after partial hepatectomy. Sham–operated rats served as controls. Pooled sera from each group of rats were analyzed by ligand blotting with 125I–insulinlike growth factor–I. Liver RNA from individual rats was analyzed by slot–blot and Northern–blot hybridization. A small decrease in the 39– to 42–kD insulinlike growth factor binding protein was apparent in sera from both the sham–operated and partial hepatectomized rats. In contrast, a dramatic increase (fivefold) in the 29–kD serum insulinlike growth factor binding protein (insulinlike growth factor binding protein–1) was apparent only in the partial hepatectomized rats. Hepatic insulinlike growth factor binding protein–1 messenger RNA abundance was significantly increased (1.99 ± 0.18–fold; p<0.05) at 1 hr, reached a peak of 2.32 ± 0.22–fold (p<0.01) at 3 hr after partial hepatectomy and returned to basal levels over the subsequent 6 to 12 hr. Interestingly, the abundance of insulinlike growth factor binding protein–1 messenger RNA was also significantly increased in the kidneys of partially hepatectomized rats at 3 hr (1.47 ± 0.23–fold; p<0.05), and peaked at 6 hr (2.50 ± 0.39–fold; p<0.05) after partial hepatectomy. No significant change in hepatic or renal insulinlike growth factor binding protein–1 messenger RNA abundance was apparent in sham–operated rats. For comparison, the abundance of the growth hormone–dependent binding protein insulinlike growth factor binding protein–3 and insulinlike growth factor–I messenger RNAs was also examined. A decrease in both hepatic insulinlike growth factor binding protein–3 and insulinlike growth factor–1 messenger RNA was observed in shamoperated and hepatectomized rats. These data demonstrate that partial hepatectomy is associated with increased expression of insulinlike growth factor binding protein–1 in both the liver and kidney. The increase in tissue and circulating insulinlike growth factor binding protein–1 may modulate the mitogenic effects of insulinlike growth factor–I during liver regeneration. (Hepatology 1992;15:1125-1131).