title: Does estrogen contribute to the hepatic regeneration following portal branch ligation in rats?
abstract: 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.
authors.affiliation: Division of Surgical Oncology, Dept of Surgery, Nagoya Univ Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawai
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawai
authors.forename: Shinya
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nimura
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000097:blood / Q000502:physiology*; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D011169:Portal Vein / Q000503:physiopathology* / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000077267:Fulvestrant; D004958:Estradiol; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase