Androgen-responsive functions of male rat liver. Effect of chronic alcohol ingestion.
Many liver processes are sexually dimorphic, and in rats, testosterone is the major steroid hormone determinant of the differing patterns of hepatic function. The microsomal content of specific enzymes and the syntheses of specific proteins are dependent on serum testosterone to maintain this dimorphism. Because the liver of male rats is strikingly androgen responsive, and because chronic alcohol ingestion decreases serum testosterone, we sought to determine whether chronic alcohol feeding would alter the masculine pattern of hepatic liver function in male rats. We quantitated both the cytosolic and nuclear forms of the hepatic androgen receptor. Alcohol feeding of male rats results in a significant loss of both types of androgen receptor sites; the specific binding capacity of both cytosolic and nuclear receptor in alcohol-fed rats is reduced to about 30% of that in either isocalorically fed rats or rats fed ad libitum. This reduction in hepatic androgen receptor activity is concomitant with a 50% reduction in serum testosterone content in the alcohol-fed animals. In addition, the activities of two hepatic androgen-responsive proteins, namely a cytosolic estrogen binder and a microsomal enzyme, estrogen 2-hydroxylase, demonstrate a decrease in activity that parallels the decreases in both forms of the androgen receptor. Administration of testosterone to the alcohol-fed animals normalized both the hepatic androgen receptor and the androgen-responsive protein activities. From these results, we conclude that chronic alcohol feeding results in a decreased androgen responsiveness of the liver, a condition that most likely results from the decreased serum testosterone levels in the alcohol-fed animals.
Eagon
P K
PK
Veterans Administration Medical Center, Pittsburgh, Pennsylvania 15240.
Willett
J E
JE
Seguiti
S M
SM
Appler
M L
ML
Gavaler
J S
JS
Van Thiel
D H
DH
D000728:Androgens / Q000502:physiology*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000502:physiology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D012727:Sex Characteristics; D013250:Steroid Hydroxylases / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000728:Androgens; D004967:Estrogens; D011944:Receptors, Androgen; D000431:Ethanol; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C020120:estrogen 2-hydroxylase