Relation of the neuroendocrine system to the development and growth of experimental mammary tumors

Abstract

The regulation of hormonal influences on mammary tumor development and growth resides in the hypothalamus. The two major hormones essential for mammary tumor development in the rat and mouse, and also for mammary tumor growth in the rat, are prolactin and estrogen. Prolactin secretion is directly controlled by the hypothalamus, and estrogen indirectly via the pituitary gonadotropins. Treatments that increase prolactin secretion in the rat and mouse increase the incidence of spontaneous mammary tumors, whereas treatments that decrease prolactin or estrogen secretion decrease the incidence of spontaneous mammary tumors in these species. In carcinogen treated rats, either an increase or decrease in prolactin or ovarian hormones inhibits development of mammary cancers. After the appearance of mammary tumors in rats, spontaneous or carcinogen-induced, a reduction in prolactin results in reduced mammary tumor growth, and an increase in prolactin in enhanced mammary tumor growth. Either a reduction in estrogen or an excess of estrogen inhibits mammary tumor growth in rats. Large doses of estrogen inhibit mammary tumor growth by preventing prolactin from stimulating tumor growth. In mice with well established mammary tumors, prolactin or estrogen have relatively little effect since these tumors are largely autonomous. In women there is inconclusive evidence as yet that prolactin plays a role in breast cancer development and growth. Women with breast cancer have normal serum prolactin levels. Regression of breast cancer after hypophysectomy may be due in part to loss of prolactin, but perhaps to loss of other pituitary hormones as well. Ovariectomy or early pregnancy have been shown to be associated with a reduced incidence of breast cancer, and either ovariectomy or treatment with high doses of estrogen can induce regression of existing breast cancer in some patients. In view of the importance of prolactin and estrogen in development and growth of mammary tumors, and in view of their direct or indirect control by the hypothalamus, it is possible that some mammary tumors have their origin in the hypothalamus.