Kalra Mamta, Mayes Jary, Assefa Senait, Kaul Anil-K, Kaul Rashmi
Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma 74107, USA.
World J Gastroenterol. 2008 Oct 21;14(39):5945-61. doi: 10.3748/wjg.14.5945.
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 ERalpha alone until 1996 when ERbeta 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.
肝细胞癌（HCC）发病率中显著的性别差异表明性激素在HCC发病机制中起重要作用。尽管相关研究早在20世纪80年代就已开始，但性激素的确切作用及其受体在HCC中的意义仍知之甚少，这可能也是目前关于HCC激素治疗潜在用途存在争议的原因。对现有文献的全面回顾揭示了在正常肝脏和HCC中关于雌激素受体（ER）和雄激素受体（AR）研究存在的几个缺点。这些缺点包括使用灵敏度较低的受体配体结合试验以及直到1996年ERβ亚型被鉴定出来之前仅针对ERα的免疫组织化学研究。用于研究的HCC动物模型主要基于化学诱导的肝癌发生，与病毒诱导的HCC发病机制相似性较低。然而，最近在肝癌细胞中的体外研究为关键细胞过程的激素调节提供了新的见解，包括ER和AR与病毒蛋白的相互作用。鉴于上述事实，迫切需要对正常肝脏和HCC中的性激素及其受体进行详细研究。在本综述中，我们系统地介绍了目前从体外、体内实验模型和临床研究中获得的关于正常肝脏和HCC中雄激素、雌激素及其受体的信息。这些信息将指导未来的基础和临床研究，以弥合知识差距，探索激素治疗在HCC中的治疗潜力。
