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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.
Authors: F J Vizoso; M Rodriguez; A Altadill; M L González-Diéguez; A Linares; L O González; S Junquera; F Fresno-Forcelledo; M D Corte; L Rodrigo Journal: World J Gastroenterol Date: 2007-06-21 Impact factor: 5.742
Authors: Mahmoud A Ali; Sahin Lacin; Reham Abdel-Wahab; Mark Uemura; Manal Hassan; Asif Rashid; Dan G Duda; Ahmed O Kaseb Journal: Onco Targets Ther Date: 2017-03-03 Impact factor: 4.147
Authors: Raphaëlle Luisier; Elif B Unterberger; Jay I Goodman; Michael Schwarz; Jonathan Moggs; Rémi Terranova; Erik van Nimwegen Journal: Nucleic Acids Res Date: 2014-01-23 Impact factor: 16.971