Androgen metabolism in regenerating liver of male rats: evidence for active uptake and utilization of testosterone

The role of androgen in the regenerative process of the liver remains unclear. Male Sprague–Dawley rats were subjected to either 70% hepatectomy or sham operation. Immediately after surgical procedures, rats were injected with 0.3 μCi/g of body weight [ 3H]-testosterone from the inferior vena cava. The radioactivities of the remnant liver were counted for 0–24 h. For measurement of sex hormones and their metabolizing enzymes activities in the regenerating liver, the same experiments were also conducted, in which the rats were sacrificed up to 120 h. The plasma and hepatic testosterone, dihydrotestosterone(DHT) and estradiol were determined by radioimmunoassays. Uptake of [ 3H]-testosterone in the regenerating liver was significantly higher during the first 6 h. 5 α-reductase I and DHT were increased in parallel to the hepatocyte proliferation which was assessed by proliferating cell nuclear antigen (PCNA) labeling index. On the other hand, hepatic 3 α-hydroxysteroid dehydrogenase level did not alter but aromatase activity significantly decreased after 70% hepatectomy. These results suggest that during the early phase of liver regeneration, testosterone was actively uptaken from the plasma by the regenerating liver and was converted into DHT by elevated hepatic 5 α-reductase enzyme. Thus androgens might play a crucial role in liver regeneration.