Hepatic stellate cells contain the functional estrogen receptor beta but not the estrogen receptor alpha in male and female rats

In an earlier study, we showed that estradiol (E2) inhibits proliferation a nd transformation in cultured rat hepatic stellate cells (HSCs) and that th e actions of E2 are mediated through estrogen receptors (ERs). This study r eports on an investigation of the cellular localization of ER subtypes ER a lpha and ER beta using immunohistochemistry in experimental fibrotic liver rats and of each ER subtype expression in cultured rat HSCs by evaluating t he produced mRNA and protein. The results indicate that high levels of ER b eta expression and low or no levels of ER alpha expression were observed in normal and fibrotic livers and in quiescent and activated HSCs from both m ales and females. The specificity of E2-mediated antiapoptotic induction th rough the ER beta was shown by dose-dependent inhibition by the pure ER ant agonist ICI 182,780 in HSCs which were undergoing early apoptosis. These fi ndings demonstrate for the first time that rat HSCs possess functional Er b eta, but not Er alpha, to respond directly to E2 exposure. (C) 2001 Academi c Press.