Submitted on August 10, 2006
Accepted on October 17, 2006
Does estrogen contribute to the hepatic regeneration following portal branch ligation in rats?
Toru Kawai1, Yukihiro Yokoyama2*, Satoru Kawai1, Shinya Yokoyama1, Koji Oda1, Tetsuro Nagasaka3, Masato Nagino1, Irshad H. Chaudry4, and Yuji Nimura1
1 Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aich, Japan
2 Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, United States; Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, United States
3 Department of Laboratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
4 Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, United States
* To whom correspondence should be addressed. E-mail: yyoko{at}med.nagoya-u.ac.jp.
The aim of this study was to determine if estrogen plays any role in the hepatic regeneration of non-ligated lobe following portal branch ligation (PBL). Male rats were subjected to PBL on left and middle lobe. Two and 7 days after PBL, the rats were sacrificed and blood and liver samples were analyzed. Sham animals underwent only laparotomy. The serum estradiol levels were significantly elevated on day 2 following PBL and returned to normal levels on day 7. The expression of estrogen receptors (ER) in the liver evaluated by Western blotting did not show any change in the non-ligated lobe compared to shams. Immunohistochemical study for ER showed a predominant ER expression in the hepatocyte nucleus in periportal area (zone 1), although there was no apparent difference in the amount and expression pattern between sham and PBL. However, chronic inhibition of ER by ER antagonist (ICI 182,780) showed a significantly lower regeneration rate of the non-ligated lobe as compared to vehicle treatment. Liver regeneration-associated genes also were less activated in ICI group. Moreover, portal venous flow, determined by fluorescent microsphere injection, was significantly lower in ICI group as compared to vehicle group. These changes correlated with the attenuated expression of eNOS mRNA both in superior mesenteric arteries and veins. In conclusion, these results indicate that the estrogen's contribution on hepatic regeneration following PBL is at least partly mediated through maintaining mesenteric blood flow by mesenteric eNOS upregulation rather than directly activating liver regeneration in the liver.
