Tejura S, Rodgers G R, Dunion M H, Parsons M A, Underwood J C, Ingleton P M
Department of Pathology, University of Sheffield Medical School.
J Mol Endocrinol. 1989 Nov;3(3):229-37. doi: 10.1677/jme.0.0030229.
The results of this study confirm our previous report of increased androgen receptor expression in livers of female SUAH Wistar rats during development of liver tumours induced by diethylnitrosamine (DENA). In adult female rats not treated with DENA, removal of the ovary increased liver androgen receptor levels but testosterone did not further enhance the androgen receptor status of ovariectomized rats. In normal adult males the testis and/or testosterone maintained high levels of androgen receptors but oestrogen reduced them in castrated rats. Oestrogen receptor levels were not significantly changed in either males or females by gonadectomy. Treatment of female rats with DENA for 10 and 16 weeks increased liver androgen receptors but oestrogen receptors were only reduced by 16 weeks of DENA treatment, whether the rats were intact or ovariectomized. Concentrations of liver androgen receptors were increased in intact and castrated male rats by 10 and 16 weeks of DENA treatment, an increase not seen in the previous experiments. Oestrogen appeared to inhibit both the increases in liver androgen receptor expression and liver tumour development in rats treated with the weakly carcinogenic dose of 10 weeks of DENA. However, the full carcinogenic dose of 16 weeks of DENA increased liver androgen receptors and decreased oestrogen receptors in female rats regardless of sex-steroid status. Development of malignant hepatocellular carcinoma (HCC) was associated with both an increase in liver androgen receptors and a decrease in oestrogen receptors. Maintenance of relatively high levels of liver oestrogen receptors appeared to protect the liver against development of HCC.
本研究结果证实了我们之前的报告，即在二乙基亚硝胺（DENA）诱导的肝肿瘤发生过程中，雌性SUAH Wistar大鼠肝脏中的雄激素受体表达增加。在未用DENA处理的成年雌性大鼠中，切除卵巢会增加肝脏雄激素受体水平，但睾酮不会进一步提高去卵巢大鼠的雄激素受体状态。在正常成年雄性大鼠中，睾丸和/或睾酮维持高水平的雄激素受体，但雌激素会降低去势大鼠的雄激素受体水平。性腺切除对雄性和雌性大鼠的雌激素受体水平均无显著影响。用DENA处理雌性大鼠10周和16周会增加肝脏雄激素受体，但雌激素受体仅在DENA处理16周后才会降低，无论大鼠是否完整或已去卵巢。DENA处理10周和16周后，完整和去势雄性大鼠肝脏雄激素受体浓度均增加，这一增加在之前的实验中未见。雌激素似乎抑制了用弱致癌剂量的DENA处理10周的大鼠肝脏雄激素受体表达的增加和肝脏肿瘤的发生。然而，16周的DENA全致癌剂量会增加雌性大鼠肝脏雄激素受体并降低雌激素受体，无论其性类固醇状态如何。恶性肝细胞癌（HCC）的发生与肝脏雄激素受体增加和雌激素受体减少均有关。维持相对较高水平的肝脏雌激素受体似乎可保护肝脏免受HCC的发生。
