We have previously hypothesized that IGF-I is a mediator of dexamethasone (DEX) effect in the newborn mouse ileum-a model designed to mimic the precocious mucosal maturation associated with spontaneous ileal perforations in extremely premature neonates. We have further investigated this hypothesis using in vivo and in vitro models of accelerated epithelial migration (a transient property, temporally associated with mucosal maturation). These experiments include a steroid-treatment model comparing IGF-I immunolocalization with bromodeoxyuridine (BrdU)-pulse-labeling, as a means of assessing epithelial cell migration, within the ileum of newborn mice that received either daily intraperitoneal injections of DEX (1 g/gm) or vehicle. Likewise, a transgenic newborn mouse model was used to compare the effect of IGF-I overexpression upon the clearance of BrdU-pulse-labeled epithelial cells traveling up the villus during the same time period. For our in vitro model, rat ileal epithelial cells (IEC-18) were cultured to confluence in serum-free media then treated with DEX, a stable IGF-I agonist, or nothing before being subjected to linear scarification. Serial photomicrographs of migrating cells were taken over time and the average speed was determined for each treatment condition. Our data demonstrate that IGF-I accelerates ileal epithelial cell migration in every model. However, DEX was only associated with accelerated epithelial cell migration in models where IGF-I (or a synthetic agonist) was highly abundant. In contrast, DEX by itself slowed migration speed in cell culture. These findings suggest that IGF-I may be a mediator of steroid effect during precocious maturation of the ileal mucosa. Normal mucosal maturation in rodents is triggered by a systemic cortisol surge that occurs during weaning (1). This process can be accelerated in suckling animals by exogenous administration of glucocorticoid in the weeks preceding weaning (2). However, administration of glucocorticoid in the first days of life results in a precocious maturation (characterized in the newborn mouse by mucosal growth concomitant with bowel wall thinning) (3). Further comparison between the precocious and the accelerated models of maturation in mouse pups reveals attenuated expression of maturation-related digestive enzymes in the younger animals (4). In addition to these developmental aberrancies, precocious maturation has also been linked to a neonatal disease state.The incidence of spontaneous ileal perforation in extremely low birth weight infants is approximately 5%, but the incidence is at least twice that when DEX is administered in the first days of life (5). Like the animal models, pathology from perforated ileal specimens demonstrates hypertrophied mucosa concomitant with a thinned bowel wall (6). Immunolocalization surveys of relevant growth factors during precocious maturation in the newborn mouse ileum have implicated two probable mediators of DEX effect (3,7,8). Whereas most growth factors are diminished by DEX treatment, IGF-I and tra...