Hypogonadism precedes liver feminization in chronic alcohol-fed male rats

Men who chronically abuse alcohol may display a spectrum of endocrine abnor malities including hypogonadism and feminization, with elevated serum estra diol and low serum testosterone. We examined factors that may result in dis ruption of hepatic sex hormone homeostasis in alcohol-fed male rats and pos sible consequences of such changes. Rats were fed alcohol-containing or iso caloric diets for 30, 60, and 90 days. In alcohol-fed rats, serum testoster one levels and hepatic activity of 2 androgen-dependent estrogen metabolizi ng enzymes were reduced (P < .05) at all times, as was activity of androgen receptor. There was also a significant early and progressive decrease in t estes/body ratio in alcohol-fed rats. Compared with this early decrease in testosterone-related parameters, there was a significant increase in serum estrogen levels (at 30 and 90 days, 132% and 168% of control values, respec tively). An increase in serum ceruloplasmin, an estrogen-responsive liver p rotein, was apparent at 60 and 90 days, but not at 30 days of alcohol expos ure, suggesting that hypogonadism precedes liver feminization. Hepatic estr ogen receptor activity was decreased in alcohol-fed rats at 60 and 90 days, the latter despite elevated serum estrogen levels. Hepatic aromatase was s lightly increased in alcohol-fed rats, an elevation probably not sufficient to account for observed increases in serum estrogen. Taken together, these data suggest that (1) alcohol induces profound reduction of serum testoste rone, resulting in loss of androgen-regulated hepatic functions such as est rogen-metabolizing enzyme activity and activity of androgen receptors; and (2) such alcohol-induced hypogonadism precedes changes in hepatic sex hormo ne homeostasis and subsequent feminization.