Role of estrogen receptor β in colonic epithelium

Several papers report that the colon is one of the tissues regulated by estrogen receptor (ER)beta. To better understand the physiological role of ER beta in colonic tissue, we have compared morphology, proliferation, and differentiation of colonic epithelium in ER beta(-/-) mice and WT littermates. BrdUrd labeling revealed that the number of proliferating cells was higher in ER beta(-/-) mice and that the migration of labeled cells toward the luminal surface was faster in ER beta(-/-) mice than in WT littermates. Additionally, in the absence of ER beta, there was a decrease in apoptosis, which was measured by immunohistochemical staining of cleaved caspase-3. The state of differentiation of the colonic epithelial cells was studied by using epithelial markers. In ER beta(-/-) mice, there was a significant decrease in the expression of the differentiation marker cytokeratin (CK)20 and in the cellular adhesion molecules alpha-catenin (an adherens junction protein) and plectin (a hemidesmosomal protein). These changes were also evident by electron microscopy as abnormalities in tight junctions and in the number and shape of desmosomes in ER beta(-/-) mice. These findings suggest a role for ER beta in the organization and architectural maintenance of the colon. Furthermore, our results indicate that the rapidly proliferating cells of the colonic epithelium in ER beta(-/-) mice are lost by increased shedding and not by increased apoptosis. In this way, hyperproliferative cells that lack ER beta do not form hyperplastic lesions and do not accumulate in the superficial epithelium.