Radiation-induced tumorigenesis of mammary glands in pituitary transplanted rats ovariectomized before onset of estrous cycle

The role of prolactin in the initiation of mammary tumorigenesis by radiation was evaluated in ovarian hormone-free rats. Rats were bilaterally ovariectomized at 23 days of age, and then, at 2.5 months of age, two pituitaries obtained from mature rats of the same strain were transplanted underneath the kidney capsule as a means of increasing the serum prolactin level to provide stimulation of development of mammary glands. After 2 weeks, the ovariectomized rats with ectopic pituitary glands were exposed to whole body irradiation of 2.6 Gy of γ-rays from a 60Co source and then treated with diethylstilbestrol as a tumor promoter. For the control, ovariectomized rats without ectopic pituitary glands were exposed and treated in the same way as the experimental group. A significant increase of serum prolactin level was observed at the time of irradiation by the pituitary transplanted rats, and intense immunohistochemical reaction with a specific anti-prolactin antiserum was detected in the ectopic pituitary glands. Also, mammary glands in the pituitary transplanted rats, ovariectomized before puberty, showed lactiferous ducts without alveolar buds at the time of tumor initiation. The pituitary transplanted rats showed a significantly increased incidence of adenocarcinoma and fibroadenoma compared with the control. Many of the mammary tumors induced in the pituitary transplanted rats given radiation were estrogen receptor (ER) (+) progesterone receptor (PgR) (+) and ER(+)PgR(−) tumors, whereas ER(−)PgR(−) tumors were mainly obtained in the control rats. In the experimental group, many of the fibroadenomas had low concentrations of ER and no PgR, while the adenocarcinomas had moderate concentrations of ER and high PgR. These results suggest that hypersecretion of prolactin from the pituitary transplants developed lactiferous ducts and accelerated the tumorigenesis of mammary glands initiated by radiation in the absence of synergism with ovarian hormones.