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 α and β determine the amount of active estrogen. In estrogen-sensitive tissues, e.g. the female breast, estrone sulfate (E1S), present at high concentrations in the circulation, is converted into the biologically active estrone (E1) by steroid sulfatase (STS) and again reverted into E1S 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 ERα and ERβ 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 ERα 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), ERβ mRNA was below the detection limit in two specimens from cholecystitis patients. To further investigate this varying expression pattern of ERβ, immunohistological studies were performed, which indeed showed low expression levels of ERβ in the damaged mucosa, while in specimens with well preserved mucosa, high ERβ 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 ERα and ERβ, these enzymes could regulate estrogen concentrations in human gallbladder.