Effect of chronic alcohol use on hepatic testosterone 5-alpha-A-ring reductase in the baboon and in the human being.

Hepatic testosterone 5-alpha-A-ring reductase (HTAR) activity was measured in open liver biopsies in eight alcohol-fed baboons and eight pair-fed controls. The animals were studied after at least 1 yr of alcohol feeding. In the alcholol-fed animals, a significant fall in enzyme activity was noted. This occurred whether the enzyme levels were related to soluble protein, to DNA, or to wet tissue weight, showing that the change was due to a decrease in the specific activity of the enzyme. In addition, aspiration liver biopsy specimens were obtained from 14 men and women with alcoholic liver disease. Again, there was a significant decrease in HTAH activity in these patients compared with a normal population. No relationship was found between hepatic histology and HTAR levels in either the baboon or human population with alcoholic liver disease, suggesting that the changes in enzyme activity were related to an alcohol effect rather than to liver disease per se. This study demonstrates that chronic alcohol use decreases the function of the enzyme which controls an important rate-limiting step in the metabolism of testosterone in the liver and that this effect may be due primarily to alcohol.