Observations on Hormonal Control of Mammary Cancer. I. Estrogen and Mammotropes2

Abstract

Groups of normal and hypophysectomized rats bearing a hormone-responsive mammary adenocarcinoma (MT.W9A) were treated with 3 and 30 μg of estradiol-17β six times weekly for 60 days and grafts of mammotropin-secreting pituitary tumor, respectively. The small dose of estradiol stimulated and the large dose inhibited the mammary tumor and the mammary gland in normal but not in hypophysectomized rats. In contrast, mammotropin was highly effective in stimulating growth of the mammary tumor, even in the hypophysectomized animals. The greatest stimulation of the mammary tumor occurred in those treated with mammotropin. Changes in mammary tumor size occurred concurrently with changes in plasma prolactin levels. With the large dose of estradiol, the pituitary glands enlarged and contained much prolactin but the plasma prolactin levels decreased. No distinct change in growth hormone values was detected in the plasma of estradioltreated rats; that of mammotropic tumor hosts rose distinctly. This is due, in part, to the greater mass of mammotropic hormone-secreting cells in the respective hosts. It is concluded that stimulation of the adult female mammary gland and of mammary tumors in rats by small doses of estrogen is indirect and results from direct (specific) stimulation of pituitary mammotropes. Large doses of estrogen inhibit growth of a hormone-responsive mammary tumor, because the stimulated mammotropes fail to release mammotropic hormone; inhibition of hormone production may follow.