Relation of Prolactin and Estrogen to Mammary Tumorigenesis in the Rat<xref ref-type="fn" rid="FN1">1</xref><xref ref-type="fn" rid="FN2">2</xref>

Abstract

In rats estrogen and prolactin are the 2 most important hormones involved in development and growth of mammary tumors. Both are controlled by the pituitary gland and hypothalamous. Ovariectomy or hypophysectomy can inhibit development of mammary tumors or can cause regression. Growth of established mammary tumors can be increased by doses of estrogen estrogen with progesterone or prolactin. Estrogen increases prolactin and growth hormone secretion by the pituitary but has no effect on tumorigenesis in the absence of the pituitary. However prolactin or prolactin with growth hormone together may promote mammary tumor development in the absence of ovaries. In an experiment to study the effects of different doses of estrogen on mammary cancer de velopment and growth in ovariectomized rats tumors were induced with 5 mg of 712-dimethylbenz (a) anthracene (DMBA) at 52 days of age. Test animals received estradiol benzoate (EB) every other day for 150 days by sc injection; controls were given only the corn oil solvent. Mammary cancers developed in all 18 controls with an average latency period of 59 days. No cancers developed in ovariectomized rats who did not receive DMBA. Greatest tumor incidence (17 of 19) occurred in rats given 2 mcg EB. Average latency was 73 days. Regression occurred in 8% of mammary tumors in intact controls but in 20% of ovariectomized rats given .2 and 2.0 mcg EB. Regression rate was 39% in ovariectomized rats given 20 mcg EB. At 150 days ovariectomized rats not treated with EB showed reduced prolactin levels; those with .2 mcg EB showed a small inc rease; the highest doses (up to 2 mcg) produced increases ranging from 11.5 to 12-fold. In rats given 2 mcg EB fewer cancers followed and the latency period was longer than in intact controls. In another experiment a large dose of estrogen given 3 months after DMBA prevented tumor growth while prolactin alone increased mammary tumor growth about 190%. EB alone completely suppressed growth of tumors whereas EB with prolactin restored growth to that of controls. Large doses of estrogen may block binding of prolactin to receptor sites or otherwise prevent prolactin from acting on tumor cells. Changes in hypothalamic function may give rise to spontaneous mammary tumors by increasing prolactin secretion especially in old female rats. Whether this applies to humans is undetermined.