Local Action of Estrone on Mammary Glands of Mice *

It has been assumed that estrogens act indirectly on the mammary glands because these hormones induce little or no growth of the breast tissues in hypophysectomized animals of most species.5s18 The results, however, have not been entirely uniform.2 Most investigators have noted an absence of mammary growth in those experiments in which hypophysectomized rats and mice have been given estrogens. ' 14.1 The simultaneous administration of extract of the hypophysis containing growth-stimulating activity and of estrogen or certain lipoidal fractions of the anterior pituitary gland has resulted in mammary growth in hypophysectomized rats and mice.6'18 These "mammogenic " extracts of the pituitary gland have been assayed by determinations of the mammary development they induce in young male mice.8 The above observations indicate that estrogens act indirectly upon the mammary glands by inducing the pituitary gland to produce a "mammogenic " substance or hormone. The absence of mammary growth in the hypophysectomized animals receiving estrogens is not adequate proof of a direct action of the pituitary gland on the breast tissues. Hypophysectomy results in many other changes in the animal, some of which may affect mammary proliferation. Estrogens are effective in extremely small amounts when applied locally to the vagina.9 ' 0 Systemic and local reactions occurred when estrogens were applied cutaneously in various solvents or carriers.' 20 The local action of estrogens on the mammary glands has indicated a direct stimulating effect in man, rabbits, and monkeys.11,12'17 The present experiments were undertaken to determine whether estrogens might act locally upon the mammary glands of mice

The Leukemogenic Action of Estrogens in Hybrid Mice *

The estrogens, a group of substances some of which are produced within the body, act much like the carcinogenic hydrocarbons under some conditions. At least five types of tumor appear among estrogen-treated mice; namely, mammary, uterine, hypophyseal, testicular, and lymphoid.8' " Other factors or influences are now known to be necessary for the realization of all of the above types of neoplasia in estrogen-treated mice except those of the uterine cervix. The additional factors or influences are those transmitted by parent or parents to their young; in other words, the tumors are strainlimited in their appearance. However, of the tumors mentioned only those of the mammary glands may appear frequently among the untreated control animals of the groups being considered at this time.24 The intrinsic humoral environments in multiparous mice of the susceptible groups are adequate to provoke mammary neoplasia. The tumors of the other glands or tissues require, for their instigation, a more drastic or a different type of stimulation; hence their infrequent spontaneous appearance among the animals studied here. The carcinogenic hydrocarbons were thought at one time to provoke tumors only in the immediately adjacent or subjacent tissues. It is now known, however, that mammary,4 ' 26 pulmonary,2 ' hepatic,25 or lymphoid5 ' 19, 20, 23 tumors may occur among mice given subcutaneous or percutaneous applications of carcinogenic hydrocarbons. Interestingly, transmitted or inherited factors also determine the nature of the response in animals given carcinogenic hydrocarbons. Carcinogens induce lymphoid tumors in mice of some strains but not in mice of other strains. In mice of strains that show a tendency to acquire lymphoid tumors spontaneously the carcinogen may increase the incidence or decrease the average age of onset of the disease. The mice of strains which show a high incidence of lymphoid tumors subsequent to estrogen treatment may not acquire suc