Effect of castration on dehydroepiandrosterone-induced hepatocarcinogenesis in male rats

Dehydroepiandrosterone (DHEA), a peroxisome proliferator, is a hepatocarcinogen in male and female rats. The incidence of DHEA-induced hepatic tumors was much higher in males compared to females, although the peroxisome proliferative effect is similar in both sexes. In this study, we have evaluated the effect of castration in male rats on DHEA-induced hepatocarcinogenesis. Orchiectomy resulted in a significant reduction in hepatocellular carcinomas (15% in castrated rats versus 81% in control rats). However, the incidence of neoplastic nodules was comparable in both orchiectomized and control groups (84% versus 94% in orchiectomized and control groups, respectively). Sixty-two percent of livers in the control group contained tumors larger than 10 mm compared to 8% in the orchiectomized group. These findings indicate that testosterone promotes the growth of neoplastic lesions induced by DHEA.