Inhibition by medroxyprogesterone acetate of precancerous mammary hyperplastic alveolar nodule formation in mice

Abstract

The effects of medroxyprogesterone acetate (MPA) on precancerous mammary hyperplastic alveolar nodule (HAN) formation in mice were studied as a possible step to evaluate the anticarcinogenic role of MPA in mammary tumors. One month of subcutaneous pellet implantation of MPA to 6-7 month-old SHN breeding mice resulted in marked decrease and increase in the numbers of HAN and ghosts (the remnants of regressed HAN), respectively. The number of HAN still tended to be smaller in the experimental mice than in the control even 1 month after removal of MPA pellets which had been implanted for 2 months. Serum prolactin level at autopsy was apparently decreased and prolonged estrous vaginal smears observed in the control were replaced by diestrus in the experimental mice. All results indicate that MPA can lastingly inhibit HAN formation in mice, and suggest that MPA acts on mammary glands both directly and indirectly through its antiestrogenic effect.

Medroxyprogesterone acetate enhances spontaneous mammary tumorigenesis and uterine adenomyosis in mice

“…In our previous paper, subcutaneous MPA pellet implantation significantly suppressed HAN formation and the effect persisted, in both 6-8 months-and 2-3 months-old SHN mice [7]. Nevertheless, in the present study, mammary tumorigenesis was enhanced by the implantation of the same size of MPA pellet as used previously, either from 1 to 3 months of age or throughout the experiment beginning at 6-8 months of age.…”

“…However, some possibilities are plausible. Firstly, while MPA suppressed HAN formation [7], the suppression was not complete, and some HAN might remain unresponsive and/or might become tolerant for the drug, then growing to tumors. The small difference or even enhancement in the number of HAN between MPA-treated and control mice in this study would support this hypothesis.…”

“…However, the information is scanty on the effects of MPA on spontaneous mammary tumors of mice, another animal model used widely and different from rat mammary tumors in cell kinetics in response to hormones [6]. We previously found that MPA suppressed the formation of preneoplastic mammary hyperplastic alveolar nodules (HAN) in a high mammary tumor strain of SHN mice, and that the effect lasted for a while [7].…”

Hormone dependence of a mouse mammary tumor line inducedin vivo by medroxyprogesterone acetate

“…In our model, the stimulatory effect of the ovaries would not depend on the same mechanism, since in MPA-treated mice pituitary hormones such as prolactin and gonadotropins are supposedly inhibited [26,32], the estrus cycle is suspended [33], and in consequence estradiol secretion is inhibited. Another clue indicating that ovarian estrogens do not stimulate tumor growth is the inhibition produced by the EB pellets, which are still able to prevent tumor progression even in the presence of physiologic serum levels.…”