Eagon P K, Willett J E, Seguiti S M, Appler M L, Gavaler J S, Van Thiel D H
Veterans Administration Medical Center, Pittsburgh, Pennsylvania 15240.
Gastroenterology. 1987 Dec;93(6):1162-9. doi: 10.1016/0016-5085(87)90240-x.
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.
许多肝脏过程存在性别差异，在大鼠中，睾酮是肝功能不同模式的主要甾体激素决定因素。特定酶的微粒体含量和特定蛋白质的合成依赖于血清睾酮来维持这种差异。由于雄性大鼠的肝脏对雄激素有显著反应，且慢性酒精摄入会降低血清睾酮水平，我们试图确定慢性酒精喂养是否会改变雄性大鼠肝脏功能的男性化模式。我们对肝脏雄激素受体的胞质和核形式进行了定量。给雄性大鼠喂食酒精会导致两种类型的雄激素受体位点显著减少；喂食酒精的大鼠中胞质和核受体的特异性结合能力降低至等热量喂食大鼠或自由进食大鼠的约30%。肝脏雄激素受体活性的这种降低与喂食酒精动物血清睾酮含量降低50%同时发生。此外，两种肝脏雄激素反应蛋白，即一种胞质雌激素结合蛋白和一种微粒体酶——雌激素2-羟化酶的活性降低，其降低程度与雄激素受体两种形式的降低程度平行。给喂食酒精的动物注射睾酮可使肝脏雄激素受体和雄激素反应蛋白的活性恢复正常。从这些结果中，我们得出结论，慢性酒精喂养导致肝脏对雄激素的反应性降低，这种情况很可能是由于喂食酒精动物血清睾酮水平降低所致。
