Pituitary hormonal imbalance is a prime etiological factor in mammary gland tumorigenesis in mice. In view of the dominant role of the hypothalamus in regulating pituitary function, hypothalamic influence on tumor induction

Continued pregnancies associated with forced breeding of intact female C3D2 F, mice increased the incidence and reduced the latent period of development of spontaneous mammary tumors. Conversely, intact virgin mice exhibited minimal sensitivity to tumor development after a lengthy latent period. Anterior and middle hypothalamic lesions significantly altered pituitary function to the extent that a number of mice in each of these groups were rendered permanently sterile. In addition, these same lesions, although not as effective as forced breeding, did increase tumor incidence and reduce the latent period of development in nulliparous and virgin mice above the level recorded in intact virgin controls. Lesions placed in the posterior hypothalamus as well as those in the anterior and middle hypothalamus that did not cause sterility were essentially ineffective in influencing tumor incidence to any greater extent than did forced breeding alone. These results indicate that enhancement of mammary tumorigenesis is related to a hormonal imbalance, neuroendocrine in origin, which probably involves the hormones prolactin and estrogen.