Interaction of estrogen and prolactin in spontaneous mammary tumorigenesis of the mouse.

Abstract

Daily treatment for 12 months of young nulliparous C3H mice with 0.1 mg 2-bromo-alpha-ergocryptine (CB-154), an effective suppressor of prolactin secretion, significantly reduced and in some instances virtually eliminated the incidence of spontaneous mammary tumors. The CB-154-treated mice had normal body weight gains and normal estrous cycles. Ovariectomy of young nulliparous C3H mice also reduced mammary tumor incicence, but appeared to be slightly less effective than treatment with the ergot. Chronic administration of 17beta-estradiol for 12-19 months (via drinking water) to young nulliparous intact or ovariectomized-hysterectomized C3H mice significantly increased mammary tumor incidence. Concurrent administration of 0.1 mg CB-154 to the estrogen-treated mice significantly reduced the incidence of mammary tumors when compared with mice treated with the steroid alone. Chronic sc administration (0.1 mg/mouse, twice weekly for 20 months) of Enovid to young, nulliparous, intact C3H mice significantly increased mammary tumor incidence, whereas concurrent administration of 0.1 mg CB-154 to the Enovid-treated mice significantly reduced the incidence of these tumors. Thus significant inhibition of spontaneous or estrogen- or Enovid-induced mammary tumorigenesis by concurrent drug-induced prolactin suppression has been demonstrated in these studies.