Response of the small intestinal mucosa to oral glucocorticoids.
These studies explored the effects of oral pharmacological doses of glucocorticoids on the normal small intestine of the adult rat. Short-term (7 days) prednisolone had little effect on mucosal structure or cell kinetics but enhanced the maximum absorptive capacities of the jejunum and ileum for galactose. This was due to an increase in carrier-mediated transport in the individual enterocytes and not to a change in the cell population. Activities of brush border enzymes were elevated and turnover studies indicated an increased rate of synthesis of brush border proteins associated with an enhanced glycoprotein content of the microvillus membrane. Subcellular fractionation studies demonstrated a large increase in the membrane-bound ribosomal RNA content of the enterocytes consistent with an enhanced synthesis of membrane proteins. These findings implicate a direct action of prednisolone on the enterocytes to increase their absorptive and digestive capacities by the induction of specific functional proteins. These effects on the absorptive and digestive functions of the small intestine were sustained with long-term (28 days) prednisolone feeding. An equivalent long-term oral dose of betamethasone-17-valerate, a locally rather than a systemically active glucocorticoid, had a similar effect on the enterocytes. However, an inhibition of crypt cell turnover resulted in a marked hypoplasia and hence no net change in the functional capacity of the mucosa. These findings emphasise the separate and opposing actions of glucocorticoids on the adult mucosa, on the one hand to stimulate enterocyte function, but on the other to reduce the enterocyte population. The predominant activity appears to be a function of each individual steroid. The predominant stimulatory action of prednisolone was further emphasised by investigating the effects of this glucocorticoid on the adapted ileum following jejunal resection. Indeed, short-term prednisolone enhanced the adaptive hyperplasia in the ideal remnant by increasing the functional capacity of the expanded population of enterocytes.
D000222:Adaptation, Physiological / Q000187:drug effects*; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001624:Betamethasone Valerate / Q000008:administration & dosage / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000187:drug effects; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D001624:Betamethasone Valerate; D011239:Prednisolone