Effect of epidermal growth factor on small intestinal sodium/glucose cotransporter-1 expression in a rabbit model of intrauterine growth retardation

Introduction: Intrauterine growth-retarded (IUGR) infants have impaired gastrointestinal function with feeding difficulties and predisposition to necrotizing enterocolitis. The rabbit provides a model of IUGR based on uterine position. Sodium/glucose cotransporter-1 (SGLT-1) is a membrane protein responsible for carbohydrate transport across the intestinal brush border membrane. Previous studies demonstrate increases in small intestinal (SI) nutrient uptake in response to amniotic fluid supplementation with epidermal growth factor (EGF). To determine whether SGLT-I expression plays a role in the intestinal response to EGF supplementation, this IUGR rabbit model was evaluated. Methods: Eight pregnant rabbits underwent placement of intraamniotic catheters into 2 normal (NI) and 2 IUGR fetuses per mother on gestational day 24. Mini-osmotic pumps infused either EGF (300 mu g/kg per day) or control solution forming 4 study groups (EGF-N1 vs Cont-N1; EGF-IUGR vs Cont-IUGR). On gestational day 31, the fetal SI was harvested. Sodium/glucose cotransporter-1/glyceraldehyde-3-phosphate dehydrogenase messenger RNA (mRNA) densitometric band ratios were measured by reverse transcriptase polymerase chain reaction. Immunohistochemistry SGLT-I staining was performed on middle SI. Statistical analysis was performed using the analysis of variance. Results: Sodium/glucose cotransporter-1 was expressed in the gastrointestinal tract throughout the last one third of gestation. There were no native differences in SGLT-I mRNA expression between NI and IUGR fetuses at term. Epidermal growth factor infusion did not significantly affect SI SGLT-1 mRNA expression in either NI or IUGR fetuses vs controls (EGF-N1 1.94 vs Cont-N1 = 1.94, P = .98; EGF-IUGR = 1.77 vs Cont-IUGR = 1.85, P = .74). Immunohistochemistry revealed increased SGLT-1 SI protein expression in infused IUGR fetuses. Conclusions: increases in previously documented up-regulation in SI nutrient transport after EGF infusion are independent of SGLT-I mRNA expression. Further studies are warranted investigating SGLT-I protein expression, localization, and functional kinetics in response to amniotic fluid supplementation with EGF. (c) 2005 Elsevier Inc. All rights reserved.