Background: After massive enterectomy, remnant intestine undergoes compensatory adaptation, A combination of human growth hormone (hGH) and a glutamine-enriched modified diet induces further adaptation in patients with short bowel syndrome (SBS) on long-term total parenteral nutrition. The specific actions of each component, however, ape not well-defined. Methods: New Zealand White rabbits were randomized to control, sham operation, of SBS (70% mid-jejunoileal resection) groups and treated with either hGH or saline. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into brush border membrane vesicles was quantitated. Serum insulin-like growth factor-I (IGF-I) levels were determined by immunoradiometric assay, Mucosal mRNA expression of IGF-I and IGF binding protein 4 (IGFBP-4) was evaluated by Northern blot analysis using rat cDNA probes. Results: Glutamine and leucine transports were 33 and 39% greater, respectively, in She hGH-treated versus saline-treated SB-S group (P < 0.05), supporting induction of system B amino acid transport. This upregulation was due, in part, to an 88% increase in glutamine carrier capacity (V-max) with no change in carrier affinity (K-m). Both hGH treatment and SBS increased serum IGF-I levels without direct correlation with increased nutrient transport. IGFBP-4 mRNA expression in small bowel mucosa of saline-treated SES animals was significantly greater than saline-treated unoperated control values, Mucosal IGFBP-4 mRNA was not significantly altered from control in the other study groups. IGF-I mRNA expression was not detected in mucosa, but weak hybridization was noted in rabbit liver. Conclusions: Human growth hormone accelerates early adaptation in SBS by upregulation of system B carrier capacity, Serum IGF-I levels and mucosal IGF-I and IGFBP-4 mRNA expression did not directly correlate with this enhanced nutrient transport, suggesting that hGH might exert its adaptive effects by mechanisms that are independent from the IGF system in this model. (C) 1991 Academic Press.