Expression of estrogen-metabolizing enzymes and estrogen receptors in cholelithiasis gallbladder

Background: Estrogen exposure is a risk factor for gallstone disease (cholelithiasis), which often leads to chronic inflammation (cholecystitis). Studies in various estrogen-sensitive tissues showed that key enzymes involved in the inactivation and activation of estrogens as well as expression of estrogen receptors a and R determine the amount of active estrogen. In estrogen-sensitive tissues, e.g. the female breast, estrone sulfate (E IS), present at high concentrations in the circulation, is converted into the biologically active estrone (E1) by steroid sulfatase (STS) and again reverted into EIS by estrogen sulfotransferase (SULT1E1) providing a local estrogen storage. Aims: To assess whether this might also apply for gallbladder epithelia, we determined expression of these two enzymes and of ER alpha and ER beta in 15 cholelithiasis specimens from tissues with/or without inflammation. Methods: Quantitative (Real-time) PCR and immunofluorescence were used as methods. Results: We demonstrate mRNA expression of SULT1E1, STS, and ERa in all specimens with mean enrichment of 3.53- vs. 1.72-fold (n.s.), 3.5- vs. 0.91-fold (n.s.), and 3.04- vs. 1.6-fold (n.s.) in the inflammatory and non-inflammatory groups, respectively. Although high expression levels were seen in many specimens (means 4.88-fold vs. 5.77-fold), ERR mRNA was below the detection limit in two specimens from cholecystitis patients. To further investigate this varying expression pattern of ERR, immunohistological studies were performed, which indeed showed low expression levels of ERR in the damaged mucosa, while in specimens with well preserved mucosa, high ERR levels were seen in the cytosol and in the nucleus. Conclusion: The data show expression of an estrogen network of activating STS and inactivating SULT1E1 Together with ER alpha and ER beta, these enzymes could regulate estrogen concentrations in human gallbladder. (c) 2008 Elsevier Masson SAS. All rights reserved.