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

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 alpha and beta 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.

To assess whether this might also apply for gallbladder epithelia, we determined expression of these two enzymes and of ERalpha and ERbeta in 15 cholelithiasis specimens from tissues with/or without inflammation.

Quantitative (Real-time) PCR and immunofluorescence were used as methods.

We demonstrate mRNA expression of SULT1E1, STS, and ERalpha 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), ERbeta mRNA was below the detection limit in two specimens from cholecystitis patients. To further investigate this varying expression pattern of ERbeta, immunohistological studies were performed, which indeed showed low expression levels of ERbeta in the damaged mucosa, while in specimens with well preserved mucosa, high ERbeta levels were seen in the cytosol and in the nucleus.

The data show expression of an estrogen network of activating STS and inactivating SULT1E1. Together with ERalpha and ERbeta, these enzymes could regulate estrogen concentrations in human gallbladder.