Effects of estradiol on liver estrogen receptor-α and its mRNA expression in hepatic fibrosis in rats

AIM:Estradiol treatment regulates estrogen receptor (ER)level in normal rat liver.However,little information is availableconcerning the role of estrogen in regulating liver ER inhepatic fibrosis in rats.The present study was conducted todetermine whether estradiol treatment in CCl4-induced liverfibrosis of female and ovariectomized rats altered liver ERαand its mRNA expression,and to investigate the possiblemechanisms.METHODS:Seventy female rats were divided into sevengroups with ten rats in each.The ovariectomy groups wereinitiated with ovariectomies and the sham operation groupswere initiated with just sham operations.The CCl4toxicfibrosis groups received 400 mL/L CCl4subcutaneously at adose of 2 mL/kg twice weekly.Estrogen groups were treatedsubcutaneously with estradiol 1 mg/kg,the normal controlgroup and an ovariectomy group received injection of peanutoil vehicle twice weekly.At the end of 8 weeks,all the ratswere killed to detect their serum and hepatic indicators,their hepatic collagen content,and liver ER and ER mRNAexpression.RESULTS:Estradiol treatment in both ovariectomy andsham ovariectomy groups reduced liver levels of ALT (from658~220 nkat/L to 311±146 nkat/L and 540±252 nkat/L to314±163 nkat/L,P<0.05) and AST (from 697±240 nkat/L to321±121 nkat/L and 631±268 nkat/L to 302±153 nkat/L,P<0.05),increased serum nitric oxide (NO) level (from53.7±17.1 μmol/L to 93.3±24.2 μmol/L and 553±23.1 μmol/Lto 87.5±23.6 Hmol/L,P<0.05) and hepatic nitric oxide synthase(NOS) activity (from 1.73±0.71 KU/g to 2.49±1.20 KU/g and1.65±0.46 KU/g to 2.68±1.17 KU/g,P<0.05),diminishedthe accumulation of hepatic collagen,decreased centrolobularnecrotic areas as well as the inflammatory reaction in ratssubjected to CCl4.The positive signal of ER and ER mRNAdistributed in parenchymal and non-parenchymal hepaticcells,especially near the hepatic centrolobular and periportalareas.Ovariectomy decreased ER level (from 10.2±3.2 to4.3±1.3) and ER mRNA expression (from 12.8±2.1 to 10.9±1.3)significantly (P<0.05).Hepatic ER and ER mRNA concentrationswere elevated after treatment with estradiol in bothovariectomy (15.8±2.4,20.8±3.1) and sham ovariectomy (18.7±3.8,23.1±3.7) fibrotic groups (P<0.05).CONCLUSION:The increase in hepatic ER and mRNAexpression may be part of the molecular mechanismsunderlying the suppressive effect of estradiol on liver fibrosisinduced by CCl4administration.