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 uncle ar. Male Sprague-Dawley rats were subjected to either 70% hepatectomy or sh am operation. Immediately after surgical procedures, rats were injected wit h 0.3 mu Ci/g of body weight [H-3]-testosterone from the inferior vena cava . The radioactivities of the remnant liver were counted for 0-24 h. For mea surement of sex hormones and their metabolizing enzymes activities in the r egenerating liver, the same experiments were also conducted, in which the r ats were sacrificed up to 120 h. The plasma and hepatic testosterone, dihyd rotestosterone(DHT) and estradiol were determined by radioimmunoassays. Upt ake of [3H]-testosterone in the regenerating liver was significantly higher during the first 6 h. 5 alpha -reductase I and DHT were increased in paral lel to the hepatocyte proliferation which was assessed by proliferating cel l nuclear antigen (PCNA) labeling index. On the other hand, hepatic 3 alpha -hydroxysteroid dehydrogenase level did not alter but aromatase activity s ignificantly decreased after 70% hepatectomy. These results suggest that du ring the early phase of liver regeneration, testosterone was actively uptak en from the plasma by the regenerating liver and was converted into DHT by elevated hepatic 5 alpha -reductase enzyme. Thus androgens might play a cru cial role in liver regeneration. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.