Eagon P K, Elm M S, Epley M J, Shinozuka H, Rao K N
Veterans Affairs Medical Center, Pittsburgh, Pennsylvania, USA.
Gastroenterology. 1996 Apr;110(4):1199-207. doi: 10.1053/gast.1996.v110.pm8613010.
BACKGROUND & AIMS: Both androgenic and estrogenic steroids have been implicated in the development and course of several liver diseases, including hepatocellular carcinoma. The aim of this study was to investigate temporal changes in hepatic estrogen and androgen receptors and hormone metabolism in a rat model of liver hyperplasia and carcinogenesis.
Rats were fed hepatocarcinogenic peroxisome proliferator agents for 3 days to 10 months. Livers were examined for proliferation markers, activity and cellular distribution of sex steroid receptors, and key enzymes in sex hormone homeostasis.
At all times, liver weight and proliferation markers in treated rats were increased. Early exposure resulted in increased nuclear estrogen and androgen receptor activity in treated rats. Tumors that developed after 9-10 months showed a marked decrease in estrogen receptor activity and, in contrast, an increase in androgen receptor activity, as did liver surrounding the tumors. Both short-term and long-term exposure to the carcinogens resulted in dramatic reductions in steroid metabolism.
This study supports the thesis that, in preneoplastic stages such as hyperplasia, there is an elevation of both receptor activities and that the progression from hyperplasia to cancer results in suppression of estrogen receptor expression but maintenance of androgen receptor.
雄激素和雌激素类甾体激素与包括肝细胞癌在内的多种肝脏疾病的发生发展过程有关。本研究旨在探讨肝脏增生和致癌大鼠模型中肝脏雌激素和雄激素受体以及激素代谢随时间的变化。
给大鼠喂食致癌性过氧化物酶体增殖剂3天至10个月。检测肝脏的增殖标志物、性类固醇受体的活性和细胞分布以及性激素稳态中的关键酶。
在所有时间点，处理组大鼠的肝脏重量和增殖标志物均增加。早期暴露导致处理组大鼠的核雌激素和雄激素受体活性增加。9至10个月后形成的肿瘤显示雌激素受体活性显著降低，相反，雄激素受体活性增加，肿瘤周围的肝脏也是如此。短期和长期接触致癌物均导致类固醇代谢显著降低。
本研究支持以下论点，即在增生等癌前阶段，两种受体活性均升高，并且从增生到癌症的进展导致雌激素受体表达受到抑制，但雄激素受体得以维持。
