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 di minish this catabolism. The effects of GH are mediated in part by insu lin-like growth factor I (IGF-I) that is produced in the liver and loc ally in GH target tissues. The aim of this study was to investigate th e effect of GH treatment on expression of the IGF-I gene and GH recept or (GHR) gene in skeletal muscle after major surgery. A new quantitati ve RT-PCR-based assay was established to measure IGF-I gene expression . Metabolically healthy patients, without significant preoperative wei ght loss, who were undergoing elective abdominal surgery were included in the study. Five patients tone woman and four men) were treated wit h daily injections of GH (0.3 IU/kg.day) in addition to being given to tal parenteral nutrition including glutamine (0.28 g/kg.day). The cont rol 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 fem oris muscle preoperatively (day 0) after induction of anesthesia. A se cond biopsy was taken under local anesthesia on postoperative day 3. T otal ribonucleic acid (RNA) was extracted from the muscle biopsies, an d IGF-I messenger RNA (mRNA) and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA and GHR mRNA levels were relat ed to the expression of a housekeeping gene (cyclophilin). In the cont rol 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 g roup (1188 +/- 400 transcripts/cpm cyclophilin on day 0 vs. 1089 +/- 3 42 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 musc le after abdominal surgery.