11 β-hydroxysteroid dehydrogenase type II in human colon: A new marker of fetal development and differentiation in neoplasms

The colon plays an important role in water and electrolyte homeostasis and is a major target tissue for aldosterone. 11β-Hydroxysteroid dehydrogenase type II enzyme (11βHSD2) confers specificity to the non-selective mineralocorticoid receptor by inactivating glucocorticoids, thus allowing binding by mineralocorticoids. Using immunohisto/cytochemistry and Northern blot analysis, we examined 11β-HSD2 expression in human fetal colon (23 cases ranging in age from 15 to 40 weeks gestation), neonatal colon (2 cases, 6 and 12 months old), normal adult colon (15), adenoma (35), adenocarcinoma (34) and the human colonic epithelial cell line T84, in the presence or absence of sodium butyrate, to study the correlation between enzyme expression and cellular or neoplastic differentiation. In fetal colon, weak 11β-HSD2 immunoreactivity was detectable in superficial epithelium from 25 weeks gestation, but normal adult levels were apparent only after 40 weeks gestation suggesting that fully developed aldosterone induced electrolyte transport can occur only at late gestational stages. In adult normal colon, superficial absorptive cells at the top of crypts were strongly positive for 11β-HSD2, whereas immunoreactivity was weak in adenomas and carcinomas, and the pattern of localization varied among patients. Northern blot analysis performed on 4 cases of adenocarcinoma also demonstrated lower levels of mRNA than autologous nonneoplastic colonic mucosa. In carcinpmas, 11β-HSD2 immunoreactivity was more frequently detected in differentiated structures, such as those forming glandular or tubular structures. Studies with T84 cells showed that expression of 11β-HSD2 was markedly enhanced with the addition of sodium butyrate, a well known inducer of cell differentiation in colonic epithelia. These results suggest that the expression of 11β-HSD2 is associated with differentiation or maturation in human colonic epithelia and that the enzyme may serve as a useful marker in development and disease.