Downregulation of nuclear sex steroid receptor activity correlates with severity of alcoholic liver injury.
Chronic ethanol ingestion in rats and humans results in significant alterations in sex steroid levels and expression of sex hormone-dependent phenotype. In this study, we used the intragastric feeding model in male rats to determine hepatic sex hormone receptor activity under circumstances of chronic ethanol exposure and differing degrees of liver injury induced by type of dietary fat. Pathological analysis and quantitation of hepatic androgen receptor (AR) and estrogen receptor (ER) activity, serum sex hormones, and sex hormone-responsive protein and mRNA expression were performed. The activity of the physiologically relevant nuclear form of both AR and ER was significantly decreased with ethanol and correlated inversely with the severity of liver injury. Serum testosterone levels, as well as expression of an androgen-dependent hepatic mRNA, were decreased by ethanol and progressive liver injury. Serum estradiol increased with liver injury. We postulate that these changes in receptor activity may be due to the oxidative stress, reduced cellular energy, and/or altered cytokine milieu known to occur in this model.
Eagon
P K
PK
Veterans Affairs Medical Center, and Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. pkeagon2@pitt.edu
Elm
M S
MS
Tadic
S D
SD
Nanji
A A
AA
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002570:Ceruloplasmin / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D015536:Down-Regulation; D004958:Estradiol / Q000097:blood; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D004041:Dietary Fats; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone; D004958:Estradiol; D002570:Ceruloplasmin