The rat undergoes profound maturational changes in the intestinal structure and function during the third week of its life. To investigate the role of peripheral glucocorticoid metabolism in this process, we studied the postnatal maturation of intestinal structure and function. The peripheral metabolism of glucocorticoids depends on enzyme 11-hydroxysteroid dehydrogenase (11HSD), which is responsible for the interconversion of corticosterone to 11-dehydrocorticosterone and thus for the modulation of glucocorticoid access to corticosteroid receptors. The pups were treated with carbenoxolone (CBX), an inhibitor of 11HSD, for 10 d during the suckling (days 8 -18) or weaning period (days 14 -24 or days 20 -30), and we determined the parameters of intestinal growth and activities of sucrase, alkaline phosphatase, and Na,K-ATPase. The CBX treatment increased plasma concentrations of corticosterone as a result of a significant reduction of peripheral degradation of corticosterone catalyzed by 11HSD. This also stimulated intestinal growth without changing somatic growth. The mucosal cell mass was significantly higher in CBX-treated suckling rats, whereas the effect of this treatment was less obvious in weanling animals. CBX increased the crypt depth and villus height in 18-and 24-d-old pups but not in 30-d-old animals. The small intestinal activities of sucrase, alkaline phosphatase, and Na,K-ATPase were not influenced by CBX. In contrast, colonic Na,K-ATPase was stimulated by CBX. We conclude that the administration of CBX results in acceleration of intestinal growth and structural maturation without any influence on the developmental pattern of brush-border hydrolases The concentration of glucocorticoids in the plasma plays an important physiologic role in the promotion of normal ontogeny of the human embryo in utero and of rodents during weaning. The rise of plasma glucocorticoids is associated with an accelerated maturation of various tissues (1). The local action of glucocorticoids in target tissues can be modified by changes in peripheral glucocorticoid metabolism. This metabolism depends on the enzyme 11-hydroxysteroid dehydrogenase (11HSD), which has been recognized to play a key role in regulating the access of glucocorticoids to corticosteroid receptors. Two isoforms of 11HSD with different properties and tissue distribution have been described. Type 2 11HSD is a high-affinity NAD-dependent isozyme that catalyzes the conversion of cortisol and corticosterone to cortisone and 11-dehydrocorticosterone, respectively, and thus decreases the local concentration of active glucocorticoids and prevents their binding to mineralocorticoid receptors. In contrast, type 1 11HSD is a NADP(H)-dependent isoform that exhibits bidirectional activity in vitro but seems to favor 11-reductase activity in intact cells. Whereas type 2 has been predominantly found in the kidney, colonic epithelium, and placenta, type 1 is the predominant type in the liver, fibroblasts, and cells of lamina propria (2).It has recently been sho...