Effects of different schedules of progesterone treatment on mammary tumorigenesis and uterine adenomyosis in SHN virgin mice.

As a possible step to estimate the factors controlling the effects of progesterone on mammary tumorigenesis, 3 groups of SHN virgin female mice were treated as follows beginning 2.5-4 months of age: Group A received the subcutaneous implantation of silastic tube containing progesterone (low dose) during the initial 4 months followed by progesterone pellet implantation (high dose) every 2 months. Group B was implanted with progesterone pellet throughout the experiment. Group C was given the vehicle only. Whereas there was little difference among groups in mammary tumorigenesis during the initial 4 months of treatments, tumorigenesis was significantly stimulated in group B thereafter. On the contrary, group A was different little from group C even after progesterone pellet implantation. The results indicate that the effects of progesterone on mammary tumorigenesis are affected by the 'preceding' progesterone conditions and that there is a critical period for manifestation of the effects of progesterone on mammary tumorigenesis, which is before 8 months of age at most. While all mice developing mammary tumors developed uterine adenomyosis in each group, the progression was enhanced by both low and high doses of progesterone.