TY - JOUR
T1 - Increased expression of insulin-like growth factor-I in serum and liver after recombinant human growth hormone administration in thermally injured rats
AU - Jeschke, Marc G.
AU - Chrysopoulo, Minas T.
AU - Herndon, David N.
AU - Wolf, Steven E.
N1 - Funding Information:
1 This study was supported by the Shriners Hospital for Children, Grant 8010 and American Heart Association Grant 96009870. 2To whom correspondence should be addressed at Shriners Hospital for Children, Medical Staff, 815 Market St., Galveston, TX 77550. Fax: 409-770-6919. E-mail: Swolf@sbi.utmb.edu.
PY - 1999/7
Y1 - 1999/7
N2 - Background. Recombinant human growth hormone (rhGH) has been shown to modulate 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, suggesting that rhGH may exert some of its effects indirectly through IGF-I stimulation. 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 scald burn were randomly divided to receive either rhGH (2.5 mg/kg/day im) or saline (control). Rats were sacrificed on postburn days 1, 2, 5, and 7 and serum IGF-I, hepatic IGF-I mRNA, and IGF-I protein concentration were measured. The physiologic response to changes in IGF-I levels was evaluated by measuring hepatocyte proliferation, total liver protein concentration, and muscle dry/wet weights. Results. Serum IGF-I was increased from postburn day 1 through day 7 in rats receiving rhGH compared to controls (P < 0.05). Hepatic IGF-I mRNA and IGF-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 increased hepatocyte proliferation at 5 days and total liver protein concentration 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. Recombinant hGH attenuated this decrease by stimulating hepatic IGF-I expression. Increases in IGF-I were associated with increases in hepatocyte proliferation and protein concentration in liver and muscle. Conclusion. We suggest that rhGH modulates the hypermetabolic response through IGF-I stimulation in the hepatic parenchyma.
AB - Background. Recombinant human growth hormone (rhGH) has been shown to modulate 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, suggesting that rhGH may exert some of its effects indirectly through IGF-I stimulation. 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 scald burn were randomly divided to receive either rhGH (2.5 mg/kg/day im) or saline (control). Rats were sacrificed on postburn days 1, 2, 5, and 7 and serum IGF-I, hepatic IGF-I mRNA, and IGF-I protein concentration were measured. The physiologic response to changes in IGF-I levels was evaluated by measuring hepatocyte proliferation, total liver protein concentration, and muscle dry/wet weights. Results. Serum IGF-I was increased from postburn day 1 through day 7 in rats receiving rhGH compared to controls (P < 0.05). Hepatic IGF-I mRNA and IGF-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 increased hepatocyte proliferation at 5 days and total liver protein concentration 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. Recombinant hGH attenuated this decrease by stimulating hepatic IGF-I expression. Increases in IGF-I were associated with increases in hepatocyte proliferation and protein concentration in liver and muscle. Conclusion. We suggest that rhGH modulates the hypermetabolic response through IGF-I stimulation in the hepatic parenchyma.
KW - Acute-phase response
KW - Burns
KW - Growth hormone
KW - Hypermetabolic response
KW - Insulin-like growth factor-I
KW - Rats
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U2 - 10.1006/jsre.1999.5623
DO - 10.1006/jsre.1999.5623
M3 - Article
C2 - 10383855
AN - SCOPUS:0032769331
SN - 0022-4804
VL - 85
SP - 171
EP - 177
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -