Mammary Carcinogenesis by 3-Methylcholanthrene. III. Induction of Mammary Carcinoma and Milk Secretion in Male Rats Bearing Ovarian Grafts2

Abstract

These experiments demonstrate that, while mammary cancers do not develop in intact male rats treated with 3-methylcholanthrene (MCA), a few tumors develop when ovaries are grafted into these rats. The tumor incidence rises markedly (14–66%) if ovaries are grafted into castrated male rats. Testicular hormones profoundly inhibit mammary carcinogenesis by 3-MCA. The histologic evidence suggests that ovarian grafts from castrated male rats are subjected to much greater pituitary stimulation than those from the non-orchiectomized males. The ovarian grafts do not survive and function as well in the intact male rats as in the castrated rats. The age of the graft is also important. Transplantation of “young” ovaries in young or old hosts is more successful than the grafting of ovaries from old rats. Grafts of ovaries of old rats are refractory to pituitary stimulation. “Lactation” in the castrated males bearing ovarian grafts is associated with marked enlargement and hyperplasia of acidophils of the pituitary gland. Our experiments support the view that acidophils secrete prolactin. Two factors are involved in the production of pituitary hyperplasia and lactation: (a) the effect of gonadectomy, and (b) the effect of estrogen produced by the ovarian grafts. The data demonstrate conclusively that in steroid hormone-dependent mammary cancer the neoplasm regresses when the steroid-producing organs, the ovarian grafts, are removed. A hyperfunctioning pituitary, while it is capable of maintaining the secretory activity of the mammary gland, is unable to sustain the growth of a dependent neoplasm in the absence of ovarian steroid hormones. These observations are analogous to those made in humans with hormone-dependent cancers.