Stimulation of lactose synthetase activity and casein synthesis in mouse mammary explants by estradiol

17 beta-Estradiol (E2; 1 ng/ml) can significantly (P less than 0.05) augment lactose synthetase activity (85%) and casein synthesis (65%) in mammary gland explants (from midpregnant C3H/HeN mice) cultured in medium 199 containing insulin, cortisol, PRL, and T3. Both T3 (0.65 ng/ml) and a physiological concentration of PRL (50 ng/ml) are required for stimulation by E2; at higher PRL levels, the effects of E2 are obscured. Sex steroid specificity was supported by the observations that the E2 effects are blocked by the antiestrogen nafoxidine (5 micrograms/ml), and that 17 alpha-estradiol (5 ng/ml) was inactive; however, at 5 ng/ml, estrone and diethylstilbestrol were equipotent to E2. Testosterone (5 micrograms/ml) and progesterone (1 microgram/ml) were inhibitory, although progesterone did not suppress casein synthesis. Since E2 did not alter the amount of epithelial DNA, its effects represent an increase in biological activities per cell. E2, therefore, in conjunction with the classical lactogenic hormones and T3 can act directly on mammary tissue by promoting differentiation.