Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Growth Hormone Treatment Prevents the Decrease in Insulin-Like Growth Factor I Gene Expression in Patients Undergoing Abdominal Surgery*

Acquired GH resistance together with reduced skeletal muscle mass are found in patients with increased protein catabolism due, for example, to sepsis, trauma, or major surgery. Both administration of glutamine-containing parenteral nutrition and GH treatment have been found to diminish this catabolism. The effects of GH are mediated in part by insulin-like growth factor I (IGF-I) that is produced in the liver and locally in GH target tissues. The aim of this study was to investigate the effect of GH treatment on expression of the IGF-I gene and GH receptor (GHR) gene in skeletal muscle after major surgery. A new quantitative RT-PCR-based assay was established to measure IGF-I gene expression. Metabolically healthy patients, without significant preoperative weight loss, who were undergoing elective abdominal surgery were included in the study. Five patients (one woman and four men) were treated with daily injections of GH (0.3 IU/kg.day) in addition to being given total parenteral nutrition including glutamine (0.28 g/kg.day). The control group consisted of eight patients (three women and five men), who were given glutamine-enriched total parenteral nutrition but no GH. A muscle biopsy was taken from the lateral portion of the quadriceps femoris muscle preoperatively (day 0) after induction of anesthesia. A second biopsy was taken under local anesthesia on postoperative day 3. Total ribonucleic acid (RNA) was extracted from the muscle biopsies, and IGF-I messenger RNA (mRNA) and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA and GHR mRNA levels were related to the expression of a housekeeping gene (cyclophilin). In the control group, IGF-I mRNA levels decreased from 1505 +/- 265 (mean +/- SEM) transcripts/cpm cyclophilin on day 0 to 828 +/- 172 on day 3 (P < 0.05). In contrast, IGF-I mRNA levels did not change in the GH-treated group (1188 +/- 400 transcripts/cpm cyclophilin on day 0 vs. 1089 +/- 342 transcripts/cpm cyclophilin on day 3). No statistically significant changes were seen in GHR expression. We conclude that administration of GH prevents the reduction in IGF-I gene expression in skeletal muscle after abdominal surgery.

[1]  J. Wernerman,et al.  Measurement of human growth hormone receptor messenger ribonucleic acid by a quantitative polymerase chain reaction-based assay: demonstration of reduced expression after elective surgery. , 1997, The Journal of clinical endocrinology and metabolism.

[2]  M. Thorén,et al.  The individual responsiveness to growth hormone (GH) treatment in GH-deficient adults is dependent on the level of GH-binding protein, body mass index, age, and gender. , 1996, The Journal of clinical endocrinology and metabolism.

[3]  L. Carlsson,et al.  Acute and chronic effects of subcutaneous growth hormone (GH) injections on plasma levels of GH binding protein in short children. , 1995, The Journal of clinical endocrinology and metabolism.

[4]  R. Ross,et al.  Acquired growth hormone resistance. , 1995, European journal of endocrinology.

[5]  T. Matte,et al.  Acute high-dose lead exposure from beverage contaminated by traditional Mexican pottery , 1994, The Lancet.

[6]  A. O’Sullivan,et al.  Diagnosis of growth-hormone deficiency in adults , 1994, The Lancet.

[7]  I. Bosaeus,et al.  Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency , 1993, Clinical endocrinology.

[8]  J. Wernerman,et al.  Biosynthetic Human Growth Hormone Preserves Both Muscle Protein Synthesis and the Decrease in Muscle‐free Glutamine, and Improves Whole‐body Nitrogen Economy After Operation , 1992, Annals of surgery.

[9]  A. Rowland,et al.  Ligand-mediated immunofunctional assay for quantitation of growth hormone-binding protein in human blood. , 1991, The Journal of clinical endocrinology and metabolism.

[10]  J. Sussenbach,et al.  Complete nucleotide sequence of the high molecular weight human IGF-I mRNA. , 1991, Biochemical and biophysical research communications.

[11]  J. Wernerman,et al.  Addition of Glutamine to Total Parenteral Nutrition After Elective Abdominal Surgery Spares Free Glutamine in Muscle, Counteracts the Fall in Muscle Protein Synthesis, and Improves Nitrogen Balance , 1989, Annals of surgery.

[12]  D. Halliday,et al.  Protein and energy metabolism with biosynthetic human growth hormone after gastrointestinal surgery. , 1987, Annals of surgery.

[13]  D. Wilmore,et al.  Positive nitrogen balance with human growth hormone and hypocaloric intravenous feeding. , 1987, Surgery.

[14]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[15]  B. Haendler,et al.  Complementary DNA for human T‐cell cyclophilin. , 1987, The EMBO journal.

[16]  Manson Jm,et al.  Positive nitrogen balance with human growth hormone and hypocaloric intravenous feeding. , 1986 .

[17]  A. Lindahl,et al.  Effects of local administration of GH and IGF-1 on longitudinal bone growth in rats. , 1986, The American journal of physiology.

[18]  J. Jansson,et al.  Growth hormone stimulates longitudinal bone growth directly. , 1982, Science.

[19]  S. Perrin,et al.  Site-specific mutagenesis using asymmetric polymerase chain reaction and a single mutant primer. , 1990, Nucleic acids research.

[20]  F. Borek.  Radioimmunoassay and Related Procedures in Medicine 1982. International Atomic Energy Agency, New York (1982), (825 pp., illus.) Price: Austrian Schillings 1350.- , 1983 .