Inhibition of mammary tumorigenesis in GR mice with 2-bromo-α-ergocryptine

Abstract

A high incidence of mammary tumors is found in multiparous GR mice during the 2nd and 3rd pregnancies and in nulliparous GR mice treated with estrone/progesterone. The purpose of this study was to determine if prolactin is a contributing hormone in the genesis of these neoplasms. In one series of experiments, 238 15‐week‐old nulliparous GR mice were treated with estrone (drinking water, 0.5 mg/liter) plus progesterone (30 mg progesterone pellet with cholesterol, implanted SC once monthly) for a period of 13 weeks. Half of these mice were injected SC once daily with 100 μg of the prolactin‐suppressing drug 2‐bromo‐α‐ergocryptine (CB‐154) for the duration of hormone treatment, and the other half were injected SC once daily with 0.9% NaCl solution (controls). In another series of experiments, 87 pregnant GR mice were divided into two groups and injected SC once daily from day 7 to 21 of pregnancy with 0.9% NaCl solution (controls) or CB‐154 (100 μg/mouse). In the first series, the numbers of mice with mammary tumors and total number of mammary tumors were: controls, 58/119 (49%) and 73; CB‐154 treatment, 34/119 (29%) and 37, respectively. In the second series, the numbers were: controls, 39/44 (89%) and 73; CB‐154 treatment, 24/43 (56%) and 43, respectively. In both studies, CB‐154 treatment significantly (p<0.05–0.005) reduced the percentage of mice with mammary tumors and total number of mammary tumors. These results provide evidence that prolactin is a contributing hormone in the genesis of estrone/progesterone and pregnancy‐induced mammary tumors in female GR mice.