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Estrogen derivatives: novel therapeutic agents for liver cirrhosis and portal hypertension

Zhang, Bin; Wu, Zhi-Yong

European Journal of Gastroenterology & Hepatology: March 2013 - Volume 25 - Issue 3 - p 263–270
doi: 10.1097/MEG.0b013e32835ab5dc
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Sex differences in the incidence of liver cirrhosis and portal hypertension have been reported by epidemiological studies. Previous studies have indicated that estrogen therapy improved hepatic fibrosis, inhibited the activation of hepatic stellate cells, and reduced portal pressure, whereas the administration of exogenous estrogens resulted in some potential risks, limiting their clinical use. However, the biological actions of estrogens are mediated by three subtypes of estrogen receptors (ERs): ERα, ERβ, and G-protein-coupled ER. These ER subtypes act in distinct ways and exert different biological effects that mediate genomic and nongenomic events, resulting in tissue-specific responses. In addition, active estrogen metabolites, with little or no affinity for ERs, could mediate the fibrosuppressive effect of estrogens through an ER-independent pathway. Taken together, such specific estrogen derivatives as ER selective agonists, or active estrogen metabolites, would provide novel therapeutic opportunities, stratifying this hormonal treatment, thereby reducing undesired side-effects in the treatment of liver cirrhosis and portal hypertension.

Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Correspondence to Zhi-Yong Wu, Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 1630 Dongfang Road, Shanghai, China Tel: +86 21 68383732; fax: +86 21 68383090; e-mail: zhiyongwu@gmail.com

Received July 25, 2012

Accepted September 24, 2012

© 2013 Lippincott Williams & Wilkins, Inc.