Protection of epithelial function in human jejunum cultured with hydrocortisone.

Over 24-h culture with hydrocortisone (400 nM), activity of brush-border alkaline phosphatase, alpha-glucosidase, and leucyl-2-naphthylamidase and cytoplasmic-mitochondrial malate dehydrogenase increased (P less than 0.05) by 80-133% compared with controls. Uptake of 3-O-methyl-D-[14C]glucose after 24-h culture was increased (P less than 0.05) by 30% compared with cultures without hydrocortisone. Labeling of protein with L-[14C]tyrosine and glycoprotein with D-[3H]glucosamine increased (P less than 0.05) by 40 and 88%, respectively, with hydrocortisone. The effects of hydrocortisone were dose dependent at normal serum concentrations (100-600 nM) and not further stimulated by larger concentrations. Cytoplasmic lactate dehydrogenase and lysosomal hexosaminidase activity, specific radioactivity of soluble precursor pools for protein and glycoprotein labeling, incorporation of [3H]thymidine into DNA, and morphology were unaffected by hydrocortisone. Inhibitors of glucocorticoid receptor binding (progesterone), mRNA transcription (alpha-amanitin), and protein synthesis (cycloheximide) prevented the effects of hydrocortisone. We suggest that hydrocortisone maintains the digestive, absorptive, and cellular function of cultured human jejunum. These protective effects were associated with increased protein synthesis and glycosylation and dependent on a classical steroid-hormone mechanism.