Increased expression of insulin-like growth factor-I in serum and liver after recombinant human growth hormone administration in thermally injured rats

Background. Recombinant human growth hormone (rhGH) has been shown to modul ate the hypermetabolic response and the hepatic acute-phase response after thermal injury. In vitro studies, however, demonstrated that rhGH activates insulin-like growth factor-I (IGF-I) gene transcription and production, su ggesting that rhGH may exert some of its effects indirectly through IGF-I s timulation. The purpose of this study was to determine the effects of rhGH on serum and hepatic IGF-I in thermally injured rats. Methods. Sprague-Dawley rats (56 males) receiving a 60% TBSA third-degree s cald burn were randomly divided to receive either rhGH (2.5 mg/kg/day im) o r saline (control). Rats were sacrificed on postburn days 1, 2, 5, and 7 an d serum IGF-I, hepatic IGF-I mRNA, and IGF-I protein concentration were mea sured. The physiologic response to changes in IG;F-I levels was evaluated b y measuring hepatocyte proliferation, total liver protein concentration, an d muscle dry/wet weights. Results. Serum IGF-I was increased from postburn day 1 through day 7 in rat s receiving rhGH compared to controls (P < 0.05). Hepatic IGF-I mRNA and IG F-I protein expression were increased from day 1 to 7 after burn in animals receiving rhGH when compared to controls (P < 0.05). Recombinant hGH incre ased hepatocyte proliferation at 5 days and total liver protein concentrati on at 5 and 7 days postburn compared to controls (P < 0.05). Muscle dry/wet weights increased in rats receiving rhGH at 7 days after burn compared to controls (P < 0.05). Summary. Liver and serum IGF-I levels decreased after a thermal injury. Rec ombinant hGH attenuated this decrease by stimulating hepatic IG;F-I express ion. Increases in IGF-I were associated with increases in hepatocyte prolif eration and protein concentration in liver and muscle. Conclusion. We suggest that rhGH modulates the hypermetabolic response thro ugh IGF-I stimulation in the hepatic parenchyma. (C) 1999 Academic Press.