CORRELATION BETWEEN SERUM PROLACTIN LEVELS AND HEPATOCELLULAR TUMORIGENESIS INDUCED BY 3'-METHYL-4-DIMETHYLAMINOAZOBENZENE IN MICE

Ovariectomy at 1 month of age promotes development of hepatocellular a denomatous nodules in female C57BL/6 x DS-F-1 mice treated neonatally with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Implantation of oestradiol-17 beta (E(2)) pellets at 1 month of age suppresses nodule development. Since E(2) increases serum levels of prolactin, high seru m levels of prolactin in mice that have received implants of E(2) pell ets may play a role in the suppression of hepatocellular tumorigenesis . Therefore, to investigate the role of prolactin in hepatocellular tu morigenesis, we examined development of adenomatous nodules in female mice that had been treated neonatally with 3'-Me-DAB and had undergone ovariectomy at 1 month of age, under various serum levels of prolacti n. Treatment of these mice with perphenazine (dopamine antagonist) fro m 6 months of age or transplantation of pituitary glands under the ren al capsule at 6 months of age markedly increased serum levels of prola ctin and significantly suppressed the incidence of adenomatous nodules at 12 months of age. Implantation of E(2) pellets at 1 month of age i ncreased serum levels of prolactin to a greater extent and further dec reased the incidence of adenomatous nodules. Treatment of mice that ha d received implants of E(2) pellets at 1 month of age with bromocripti ne (dopamine agonist) from 6 months of age decreased serum levels of p rolactin, and was accompanied by an increase in the incidence of nodul es. The present results showed that an increase in serum levels of pro lactin was accompanied by a decrease in incidence of liver tumours ind uced by 3'-Me-DAB in mice, suggesting a suppressive effect of prolacti n on liver tumorigenesis in mice. Thus, it is possible that the suppre ssive effect of oestrogen on liver tumorigenesis in mice is mediated, at least in part, by prolactin.