The increased estrogen-induced lobuloalveolar structures in mammary tissues constitutively expressing cyclin D1 were blocked by a progesterone antagonist, enhanced when progestins were added to estrogen, and did not appear in response to progestins alone. (A to H) Mifepristone blocks estrogen effects in cyclin D1-expressing mice. The effect of treatment using continuous-release estradiol pellets was compared to the effect of treatment using estrogen plus continuous-release mifepristone (RU486) in wild-type mice (A and C versus E and G) and MMTV-cyclin D1 mice (B and D versus F and H) 2 months after pellet implantation at 2 months of age. Mammary glands were harvested for analysis using whole-mount preparations (×10) (A, B, E, and F) and for routine hematoxylin and eosin staining histology (×40) (C, D, G, and H). (I to P) Progestins enhance estrogen's effects on mammary tissues constitutively expressing cyclin D1. The effect of the combination of progesterone pellets with continuous-release estradiol pellets was compared to the effect of progesterone pellets alone in wild-type mice (I and K versus M and O) and MMTV-cyclin D1 mice (J and L versus N and P) 2 months after pellet implantation. Mammary glands were harvested from mice 4 months of age for analysis by whole-mount preparations (×10) (I, J, M, and N) and for routine hematoxylin and eosin staining histology (×40) (K, L, O, and P).