Epidermal growth factor and human growth hormone accelerate adaptation after massive enterectomy in an additive, nutrient-dependent, and site-specific fashion

Abstract

Background . After massive enterectomy (ME), remnant intestine undergoes compensatory adaptation. Epidermal growth factor (EGF) and human growth hormone (hGH) have each been shown to enhance total length small intestine nutrient transport after ME. This study aims to determine the differential effects of EGF and hGH on proximal and distal small intestinal remnants after ME. Methods . New Zealand white rabbits underwent 70% mid-jejunoileal resection. After 1 week, animals received hGH (0.2 mg/kg/day), EGF (1.5 μg/kg/hr), hGH + EGF, or vehicle (equal volume) for 7 days. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into brush border membrane vesicles was quantitated. Serum insulin-like growth factor-I concentrations as well as proximal and distal villus and microvillus heights were measured. IGF binding protein-3 and -4 mRNA expression was determined in full-thickness proximal and distal gut remnants. Results . Concomitant hGH and EGF treatment up-regulates glucose (100%), glutamine (80%), and leucine (60%) transport in the proximal remnant; alanine (150%) and arginine (400%) transport in the distal remnant; and microvillus height (25% to 35%) both proximally and distally. Serum IGF-I levels and gross villus heights were not different among groups. Conclusions . Co-infusion of hGH and EGF accelerates intestinal adaptation after ME in an additive, nutrient-dependent, and site-specific fashion via enhanced nutrient transport as well as microvillus hypertrophy.