Estrogen Accelerates Cell Proliferation through Estrogen Receptor α during Rat Liver Regeneration after Partial Hepatectomy

Although estrogen is implicated in the regulation of cell growth and differentiation in many organs, the exact mechanism for liver regeneration is not completely understood. We investigated the effect of estrogen on liver regeneration in male and female Wistar rats after 70% partial hepatectomy (PHx) and performed immunohistochemistry, western blotting and Southwestern histochemistry. 17 beta-estradiol (E-2) and ICI 182,780 were injected into male rats on the day before PHx. The proliferating cell nuclear antigen (PCNA) labeling index reached a maximum at 48 hr after PHx in males, and at 36 hr in females and E-2-treated male rats. Estrogen receptor a (ERa) was expressed in zones 1 and 2 in male rats, but was found in all zones in female rats. Interestingly, ERa was not detected at 6-12 hr after PHx but was found at 24-168 hr in male rats. However, ERa expression was found at all sampling time-points in female and E-2-treated male rats. The activity of estrogen responsive element binding proteins was detected from 12 hr after PHx in male rats but was found from 6 hr in female and E-2-treated male rats. ERa was co-expressed with PCNA during liver regeneration. These results indicate that estrogen may play an important role in liver regeneration through ERa.