Estrogen induces estrogen receptor alpha expression and hepatocyte proliferation in the livers of male mice

Estrogens play pivotal roles in sexual development, growth, reproduction, and sex differentiation and have been implicated in a number of physiological processes in various tissues. Most of the effects of estrogens are mediated by the estrogen receptors alpha (ER), beta (ER), and G protein-coupled receptor 30 (GPR30). The liver is known to be a target tissue for estrogen signaling, but the physiological role of this signaling is not well characterized. Through analyses of an estradiol (E2)-treated hepatocyte cell line and mice, we showed that E2 signaling controls hepatocyte proliferation. Importantly, our data showed that the E2 signaling that is mediated through ER is crucial for efficient liver regeneration after partial hepatectomy (PH). PH rapidly induced marked increases in circulating E2 and ER transcripts in periportal hepatocytes, well before the onset of hepatocyte proliferation. Taken together, our results indicate that increased E2 is one of the initiating signals that trigger liver regeneration. We suggest that E2 treatment could be beneficial for stimulating liver regeneration in humans.