Dexamethasone inhibits mucosal adaptation after small bowel resection

The present study examined the effects of dexamethasone on mucosal adaptation after massive small bowel resection. Rats underwent 80% jejunoileal resection or a sham operation and received either vehicle or 128 micrograms.kg-1.day-1 sc dexamethasone for 7 days. Dexamethasone infusion resulted in decreased weight, DNA content, and protein content in the duodenojejunal and ileal mucosa in both sham and resected rats. Sucrase, lactase, and maltase activities (all in mumol.g protein-1.min-1) in the duodenojejunal mucosa were elevated by dexamethasone infusion. By contrast, enzyme activities were elevated only in the ileal mucosa of dexamethasone-infused sham-operated rats compared with sham-operated control rats, and dexamethasone did not elevate enzyme activities in resected rats. We further examined whether the inhibitory effects of dexamethasone on mucosal adaptation may be related to changes in either insulin-like growth factor (IGF) or IGF binding protein (BP) serum levels. Serum IGF-I and IGF-II levels were markedly decreased in dexamethasone-infused resected and sham-operated rats. IGF BP-1 serum levels were elevated by dexamethasone treatment with a concomitant depression in serum IGF BP-2 levels. IGF BP-3 levels were lowered by dexamethasone treatment in sham-operated rats and by gut resection, and serum IGF BP-4 levels did not change. These results suggest that the growth-inhibiting effects of dexamethasone in small intestinal mucosa may be partially mediated by decreased serum IGF levels or by alterations in IGF activity associated with changes in serum levels of IGF BPs.