Metabolism of corticosterone in mammalian and avian intestine

11␤-hydroxysteroid dehydrogenase (11␤HSD) catalyzes the conversion of the glucocorticoids, corticosterone and cortisol, to the respective derivatives 11-dehydrocorticosterone and cortisone. The recent findings underline the importance of this enzyme in excluding glucocorticoids from mineralocorticoid receptors. In the present study, 11␤HSD activity was compared in the intestine of herbivorous (guinea pig), omnivorous (rat), and granivorous (hen) animals, i.e., in animals in which the Na ؉ transport either is or is not regulated by aldosterone under normal conditions and in which the plasma levels of individual glucocorticoids are different. Slices of various intestinal segments were incubated in the presence of corticosterone or 11-dehydrocorticosterone, and the steroids were extracted and analyzed by HPLC. In the mammalian intestine, the activity of 11␤HSD was very low (approaching zero) in aldosterone-insensitive segments (duodenum, jejunum) but significant activity was revealed in aldosterone-sensitive segments (ileum, cecum, and proximal and distal colon). In comparison with the rat, the guinea pig large intestine exhibited significantly higher activity of 11␤HSD. There was no detectable reductase activity (conversion of 11-dehydrocorticosterone to corticosterone) in any intestinal segments of either species. Unexpectedly, no 11␤HSD activity was observed in the avian intestine. It was found that, in contrast to the mammalian intestine, corticosterone was metabolized to 20-dihydrocorticosterone while 11-dehydrocorticosterone was converted to 11-dehydro-20-dihydrocorticosterone. The distribution of 20-hydroxysteroid dehydrogenase (20HSD) activity in the avian intestine was homogenous along the intestine and did not correlate with the mineralocorticoid sensitivity of intestinal segments. To trace different cosubstrate dependence of 11␤HSD and 20HSD, homogenates of ileum and distal colon were incubated with NAD ؉ /NADH or NADP ؉ / NADPH, respectively. In accordance with slice experiments mammalian intestine displayed only oxidation of corticosterone to 11-dehydrocorticosterone and NAD ؉ preference. In avian intestine, the metabolite formed from corticosterone was 11-dehydrocorticosterone in the presence of NAD ؉ or NADP ؉ whereas in the presence of NADPH 11-dehydro-20-dihydrocorticosterone and 20-dihydrocorticosterone were formed. Given the wide similarity between mineralocorticoid regulation of epithelial transport in mammals and birds, the unexpected finding of differences in the metabolism of corticosterone suggests that role of 20HSD is to allow aldosterone occupancy of mineralocorticoid receptors. 1998 Academic Press The enzyme 11␤-hydroxysteroid dehydrogenase (11␤HSD) interconverts active glucocorticoids (cortisol, corticosterone) to their 11-dehydro forms (cortisone, 11-dehydrocorticosterone), which normally exhibit very weak corticosteroid activity in vivo. There is now considerable evidence suggesting that 11␤HSD decreases the concentration of intracellular glucocorticoids to levels that allow aldosterone to occupy nonselective mineralocorticoid receptor