Mammary fat pad may be a potential site for initiation of estrogen action in normal mouse mammary glands

The effect of estradiol (E2) on mammary and uterine DNA synthesis has been examined in castrated virgin mice. In both these target tissues for E2, in vitro incorporation of thymidine into DNA begins 12 h after E2 treatment, and by 24 h there is approximately a 3-fold increase in the mammary glands and a 9-fold increase in the uterus. Whereas in the uterus by 48 h after E2 the rate of DNA synthesis has basically returned to control values, in the mammary gland a maximal stimulation of DNA synthesis is observed at this time, and even at 72 h after E2 there is still approximately a 2-fold increase in DNA synthesis. In vivo histoautoradiography reveals that, unlike in the uterus, 24 h after E2 there is virtually no uptake of labeled thymidine in the mammary epithelium; the increase in the uptake of thymidine is now mostly confined to the mammary adipose and connective tissues. However, 48 and 72 h after E2 there is extensive labeling of the mammary epithelium in addition to the adipose and connective tissues. These data lead us to suggest that both the mammary fat pad and epithelium are responsive to E2, and that, at least with respect to mammary cell proliferation, the mammary fat pad may be the site of initiation of estrogen action.