The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) prevents the binding of corticosterone to mineralocorticoid receptors by reversible conversion of biologically active corticosterone to inactive 11-dehydrocorticosterone. To clarify the relationship between high plasma concentrations of corticosterone during weaning and high activity of intestinal transport pathways that are induced by aldosterone in immature intestine, we have studied the distribution, developmental pattern and regulation of 11 beta-OHSD in intestinal segments that possess mineralocorticoid target epithelium. Dehydrogenase activity was already high in the caecum, and the proximal and distal colon on the second postnatal day and altered little until adulthood. In contrast, the activity in the ileum was low during the first two weeks of life, rose more than 5-fold in the next 20 days to attain a peak in 30-day-old rats, and thereafter declined to the values of adult animals. There was no significant reductase activity (conversion of 11-dehydrocorticosterone to corticosterone) in any intestinal segment of young and adult rats. The regulation of intestinal 11 beta-OHSD by corticosteroids and thyroid hormones was studied in the ileum and distal colon. In weanling rats, adrenalectomy or a high-salt diet decreased 11 beta-OHSD activities in both intestinal segments whereas dexamethasone administration prevented this decline in adrenalectomized rats and administration of deoxycorticosterone acetate led to a significant increase of intestinal 11 beta-OHSD activities in rats kept on a high-salt diet. Dexamethasone administration to intact adult rats also stimulated 11 beta-OHSD activity in the ileum and distal colon. The changes in thyroid status of weanling rats did not change the 11 beta-OHSD activities. We conclude that (1) the developmental patterns of 11 beta-OHSD activity in the small and large intestine are not identical and this discrepancy may facilitate the maturation effect of glucocorticoids in the small intestine and the stimulatory effect of aldosterone in the large intestine and (2) corticosteroids but not thyroid hormones can modulate 11 beta-OHSD activity in the developing intestine.

Institute of Physiology Czech Academy of Sciences Prague Czech Republic

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Glucocorticoid availability in colonic inflammation of rat