Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro

Background-Hepatic stellate cells play a key role in the pathogenesis of he patic fibrosis. Aims-To examine the inhibitory effect of oestradiol on stellate cell activa tion. Method-In vivo, hepatic fibrosis was induced in rats by dimethylnitrosamine or pig serum. In vitro, rat stellate cells were activated by contact with plastic dishes resulting in their transformation into myofibroblast-like ce lls. Results-In the dimethylnitrosamine and pig serum models, treatment with oes tradiol at gestation related doses resulted in a dose dependent suppression of hepatic fibrosis with restored content of hepatic retinyl palmitate, re duced collagen content, lower areas of stellate cells which express alpha s mooth muscle actin (alpha-SMA) and desmin, and lower procollagen type I and III mRNA levels in the liver. In cultured stellate cells, oestradiol inhib ited type I collagen production, alpha-SMA expression, and cell proliferati on. These findings suggest that oestradiol is a potent inhibitor of stellat e cell transformation. Conclusion-The antifibrogenic role of oestradiol in the liver may contribut e to the sex associated differences in the progression from hepatic fibrosi s to cirrhosis.