Review
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 21, 2008; 14(39): 5945-5961
Published online Oct 21, 2008. doi: 10.3748/wjg.14.5945
Role of sex steroid receptors in pathobiology of hepatocellular carcinoma
Mamta Kalra, Jary Mayes, Senait Assefa, Anil K Kaul, Rashmi Kaul
Mamta Kalra, Jary Mayes, Senait Assefa, Anil K Kaul, Rashmi Kaul, Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma 74107, United States
Correspondence to: Rashmi Kaul, PhD, Associate Professor of Immunology, Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, 1111 W 17th street, Tulsa, Oklahoma 74107, United States. rashmi.kaul10@okstate.edu
Telephone: +1-918-5611231 Fax: +1-918-5615798
Received: May 8, 2008
Revised: September 16, 2008
Accepted: September 23, 2008
Published online: October 21, 2008
Abstract

The striking gender disparity observed in the incidence of hepatocellular carcinoma (HCC) suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor (ER) and androgen receptor (AR) in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.

Keywords: Sex hormones; Estrogen receptor; Androgen receptor; Hepatocellular carcinoma; Hepatocarcinogenesis