Ostrowski J L, Ingleton P M, Underwood J C, Parsons M A
Department of Pathology, University of Sheffield Medical School, United Kingdom.
Gastroenterology. 1988 May;94(5 Pt 1):1193-200. doi: 10.1016/0016-5085(88)90012-1.
This study investigated the relationship between liver tumor development and androgen-receptor expression in diethylnitrosamine hepatocarcinogenesis in Wistar rats (SUAH substrain). Random liver samples were assayed by an isoelectric focusing method, with [3H]mibolerone as androgenic radioligand. After 16 wk of oral diethylnitrosamine treatment there was a greater than 20-fold increase in hepatic androgen receptor concentration in female rats (control group 0.3 +/- 0.07 fmol/mg cytosol protein; test group 8.36 +/- 0.96 fmol/mg cytosol protein; p less than 0.001, unpaired Student's t-test). This coincided with, and may be related to, an accelerated development of neoplastic nodules or hepatocellular carcinoma, or both. Male rats showed slower tumor development and no change in androgen receptor concentrations. This model is the first to demonstrate significantly increased androgen sensitivity in experimental hepatic carcinogenesis analogous to increased androgen receptor expression in human hepatocellular carcinoma. It may provide insight into steroid hormone sensitivity in developing tumors, and a means of testing potential therapeutic use of hormonal manipulation in human liver cancer.
本研究调查了在Wistar大鼠（SUAH亚系）的二乙基亚硝胺诱导肝癌发生过程中，肝脏肿瘤发展与雄激素受体表达之间的关系。采用等电聚焦法，以[3H]美勃酮作为雄激素放射性配体，对随机选取的肝脏样本进行检测。经口服二乙基亚硝胺处理16周后，雌性大鼠肝脏雄激素受体浓度增加了20倍以上（对照组为0.3±0.07 fmol/mg胞浆蛋白；试验组为8.36±0.96 fmol/mg胞浆蛋白；p<0.001，采用不成对学生t检验）。这与肿瘤结节或肝细胞癌的加速发展同时出现，且可能与之相关。雄性大鼠的肿瘤发展较慢，雄激素受体浓度没有变化。该模型首次证明在实验性肝癌发生过程中雄激素敏感性显著增加，类似于人类肝细胞癌中雄激素受体表达的增加。它可能为了解肿瘤发生过程中类固醇激素的敏感性提供线索，并为测试激素调控在人类肝癌中的潜在治疗用途提供一种方法。
