DEXAMETHASONE INHIBITS MUCOSAL ADAPTATION AFTER SMALL-BOWEL RESECTION

The present study examined the effects of dexamethasone on mucosal ada ptation after massive small bowel resection. Rats underwent 80% jejuno ileal resection or a sham operation and received either vehicle or 128 mu g.kg(-1).day(-1) sc dexamethasone for 7 days. Dexamethasone infusi on resulted in decreased weight, DNA content, and protein content in t he duodenojejunal and ileal mucosa in both sham and resected rats. Suc rase, lactase, and maltase activities (all in mu mol.g protein(-1)min( -1)) in the duodenojejunal mucosa were elevated by dexamethasone infus ion. By contrast, enzyme activities were elevated only in the ileal mu cosa of dexamethasone-infused sham-operated rats compared with sham-op erated control rats, and dexamethasone did not elevate enzyme activiti es in resected rats. We further examined whether the inhibitory effect s of dexamethasone on mucosal adaptation may be related to changes in either insulin-like growth factor (IGF) or IGF binding protein (BP) se rum levels. Serum IGF-I and IGF-II levels were markedly decreased in d examethasone-infused resected and sham-operated rats. IGF BP-1 serum l evels were elevated by dexamethasone treatment with a concomitant depr ession in serum IGF BP-2 levels. IGF BP-3 levels were lowered by dexam ethasone treatment in sham-operated rats and by gut resection, and ser um IGF BP-4 levels did not change. These results suggest that the grow th-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.