Recombinant human growth hormone (rhGH) downregulates hepatocyte growth factor (HGF) in burns

M. G. Jeschke, Steven Wolf, M. A. DebRoy, D. Jarrar, David Herndon

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Introduction. 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). Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)11-16
Number of pages6
JournalJournal of Surgical Research
Volume76
Issue number1
DOIs
StatePublished - Apr 1998

Fingerprint

Hepatocyte Growth Factor
Human Growth Hormone
Burns
Growth Hormone
Down-Regulation
Serum Albumin
Wounds and Injuries
Sprague Dawley Rats
Therapeutics
Proteins
Tokyo
Liver
Allergy and Immunology
Albumins

Keywords

  • Acute phase response
  • Albumin
  • Burns
  • Hepatocyte growth factor
  • Recombinant human growth hormone

ASJC Scopus subject areas

  • Surgery

Cite this

Recombinant human growth hormone (rhGH) downregulates hepatocyte growth factor (HGF) in burns. / Jeschke, M. G.; Wolf, Steven; DebRoy, M. A.; Jarrar, D.; Herndon, David.

In: Journal of Surgical Research, Vol. 76, No. 1, 04.1998, p. 11-16.

Research output: Contribution to journalArticle

Jeschke, M. G. ; Wolf, Steven ; DebRoy, M. A. ; Jarrar, D. ; Herndon, David. / Recombinant human growth hormone (rhGH) downregulates hepatocyte growth factor (HGF) in burns. In: Journal of Surgical Research. 1998 ; Vol. 76, No. 1. pp. 11-16.
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title = "Recombinant human growth hormone (rhGH) downregulates hepatocyte growth factor (HGF) in burns",
abstract = "Introduction. 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). Conclusion. 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.",
keywords = "Acute phase response, Albumin, Burns, Hepatocyte growth factor, Recombinant human growth hormone",
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T1 - Recombinant human growth hormone (rhGH) downregulates hepatocyte growth factor (HGF) in burns

AU - Jeschke, M. G.

AU - Wolf, Steven

AU - DebRoy, M. A.

AU - Jarrar, D.

AU - Herndon, David

PY - 1998/4

Y1 - 1998/4

N2 - Introduction. 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). Conclusion. 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.

AB - Introduction. 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). Conclusion. 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.

KW - Acute phase response

KW - Albumin

KW - Burns

KW - Hepatocyte growth factor

KW - Recombinant human growth hormone

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DO - 10.1006/jsre.1998.5261

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