Recombinant human growth hormone (rhGH) downregulates hepatocyte growth factor (HGF) in burns.
BACKGROUND
Hepatocyte growth factor (HGF) and recombinant human growth hormone (rhGH) have both been shown to increase albumin serum concentrations after major injury. However, the effect of rhGH on HGF production after injury is unknown. We postulated that rhGH effects constitutive protein concentrations by inducing HGF expression.


METHODS
In order to determine a dose response, 20 male Sprague-Dawley rats received three different concentrations of rhGH 1, 2.5, and 5 mg/kg and a saline treatment. Rats were sacrificed 10 days after burn and serum albumin and HGF plasma concentrations were measured. Eighty male Sprague-Dawley rats received a 60% TBSA third-degree scald burn injury and were randomly divided into three groups, control, burn plus saline treatment, or burn plus rhGH treatment (2.5 mg/kg SQ qD). Rats were sacrificed 2, 5, 7, and 14 days after burn, and serum albumin, plasma, and hepatic tissue HGF concentrations were determined (ELISA, Institute of Immunology, Tokyo, Japan).


RESULTS
At 10 days postburn serum albumin levels were significantly increased with rhGH 2.5 mg/kg treatment (P < 0.05); however, HGF plasma concentrations were significantly decreased with a dose of 5 mg/kg of rhGH compared to control and rhGH 1.0 mg/kg (P < 0.05). Serum albumin concentrations decreased immediately after burn and remained low until at least the 14th day after injury. RhGH-treated animals had higher levels of albumin on Day 7 after burn (P < 0.05). Plasma HGF levels decreased immediately after burn, but increased after the second day postburn. Beginning on the 5th day after injury, HGF levels in non-rhGH-treated rats were significantly higher compared to those in rhGH-treated rats (P < 0.05). Hepatic tissue HGF concentrations were higher in non-rhGH-treated rats compared to rhGH treated animals 7 days after burn (P < 0.01).


CONCLUSIONS
Although rhGH treatment improves constitutive protein synthesis, rhGH decreases HGF concentration in a dose-dependent manner. The improvements in constitutive protein concentrations do not occur via a HGF dependent pathway.
Jeschke
M G
MG
Shriners Burns Hospital, Galveston, Texas 77550, USA.
Wolf
S E
SE
DebRoy
M A
MA
Jarrar
D
D
Herndon
D N
DN
D000210:Acute-Phase Reaction / Q000188:drug therapy / Q000503:physiopathology*; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002056:Burns / Q000188:drug therapy / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000097:blood*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000096:biosynthesis
D012709:Serum Albumin; D017228:Hepatocyte Growth Factor; D013006:Growth Hormone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase