Estradiol accelerates liver regeneration through estrogen receptor α

Abstract

Background: We previously demonstrated that liver resection triggers estradiol production, which, in turn, induces the proliferation of hepatocytes to promote liver regeneration in mice. In this study, we demonstrated estradiol-induced estrogen receptor alpha (ERα) expression.

Methods: To further explore the role of ERα in estradiol-mediated liver regeneration, in the present study, we confirmed impaired liver regeneration ability in ERα knockout mice.

Results: Further analysis during liver regeneration revealed a role for ERα in hepatic steatosis, tumor necrosis factor-alpha and interleukin 6 expression, and nuclear factor-κB and signal transducer and activator of transcription 3 DNA-binding activities.

Conclusion: Moreover, estradiol administration accelerated liver regeneration through ERα, indicating the feasibility of the estrogen-ERα axis as a target for accelerating the rate of liver regeneration.

Keywords:

• estrogens
• estrogen receptor α; ERα
• partial hepatectomy
• liver regeneration

Acknowledgments

We are grateful to our department members at the National Center for Geriatrics and Gerontology (NCGG) for their helpful discussions. This work was supported by a Grant-in-Aid from NCGG (28-25 and 19-27), the Japan Science and Technology Agency (A-STEP-AS2312036G and FY2013-SICP), and the Ministry of Education, Culture, Sports, Science and Technology (MEXT 18659493).

Data sharing statement

The data used to support the findings of this study are available from the corresponding author upon request.

Disclosure

The authors report no conflicts of interest in this work.