Stimulation of mammary tumourigenesis and inhibition of uterine adenomyosis by suppressed progesterone effects in SHN mice

Abstract

It has been shown in mice that progesterone stimulates both mammary tumourigenesis and uterine adenomyosis in intact animals in the presence of normal levels of prolactin and oestrogen. From the view-point of the high dependence of progesterone upon other hormones, the effects of suppressed progesterone action on mammary and uterine lesions were studied in this paper. Subcutaneous implantation of RU 486, an antiprogesterone, enhanced preneoplastic and neoplastic mammary gland growth in SHN virgin mice associated with elevated plasma prolactin levels and continued vaginal oestrous stage. This mammary gland growth stimulated by RU 486 was arrested by additional treatment with progesterone. On the contrary, RU 486 treatment markedly suppressed the development of uterine adenomyosis, which was counteracted only by progesterone supplement for a long period in old mice. The previous and the present findings conclude that progesterone stimulates mammary tumourigenesis by acting synergistically with prolactin and oestrogen when the latter hormones are at normal levels, but it prevents tumourigenesis by acting antagonistically with high levels of prolactin and oestrogen. They further confirmed the importance of progesterone in the development of adenomyosis, while its relationship with prolactin and oestrogen is not understood so well as it is in mammary tumourigenesis.