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Am J Physiol Gastrointest Liver Physiol 292: G582-G589, 2007. First published October 19, 2006; doi:10.1152/ajpgi.00374.2006 Free Article
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HORMONES AND SIGNALING

Does estrogen contribute to the hepatic regeneration following portal branch ligation in rats?

Toru Kawai,1 Yukihiro Yokoyama,1,3 Satoru Kawai,1 Shinya Yokoyama,1 Koji Oda,1 Tetsuro Nagasaka,2 Masato Nagino,1 Irshad H. Chaudry,3 and Yuji Nimura1

1Division of Surgical Oncology and Department of Surgery, 2Department of Laboratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan; and 3Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Alabama

Submitted 10 August 2006 ; accepted in final form 17 October 2006

The aim of this study was to determine whether estrogen plays any role in the hepatic regeneration of nonligated lobe following portal branch ligation (PBL). Male rats were subjected to PBL on the left and middle lobes. Two and 7 days after PBL, the rats were killed 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 nonligated lobe compared with 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 an ER antagonist (ICI 182,780) showed a significantly lower regeneration rate of the nonligated lobe compared with vehicle treatment. Liver regeneration-associated genes also were less activated in the ICI group. Moreover, portal venous flow, determined by fluorescent microsphere injection, was significantly lower in the ICI group compared with vehicle group. These changes correlated with the attenuated expression of endothelial nitric oxide synthase mRNA in both 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 endothelial nitric oxide synthase upregulation rather than directly activating liver regeneration in the liver.

portal vein embolization; nonligated lobe; estrogen receptor; endothelial nitric oxide synthase; mesenteric flow


Address for reprint requests and other correspondence: Y. Yokoyama, Division of Surgical Oncology, Dept. of Surgery, Nagoya Univ. Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan (e-mail: yyoko{at}med.nagoya-u.ac.jp)






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