A possible mechanism for increased breast cell proliferation by progestins through increased reductive 17β‐hydroxysteroid dehydrogenase activity

Abstract

We have investigated whether progestins may be able to regulate breast cell proliferation by altering the fraction of oestradiol relative to oestrone, using the human breast cancer cell line MCF-7. The ability of the two oestrogens, oestradiol and oestrone, to stimulate breast tumour cell proliferation was investigated. Oestradiol in concentration was of 10-fold greater proliferative potency than oestrone. The progestin MPA increased both reductive and oxidative 17 beta-hydroxysteroid oxidoreductase activity when the tissue culture media pH indicator phenol red was included in the media. When phenol red was excluded from the tissue culture media, MPA increased predominantly the reductive 17 beta-hydroxysteroid oxidoreductase activity, and to a far greater extent than in the presence of phenol red. Other progestins such as levonorgestrel, norethisterone and norethisterone acetate also increased predominantly reductive 17 beta-hydroxysteroid oxidoreductase activity in the absence of phenol red. The action of MPA on reductive 17 beta-hydroxysteroid oxidoreductase activity was increased by treatment with oestradiol to a small but significant extent. We propose that the progestational increase of reductive 17 beta-hydroxysteroid oxidoreductase activity is a possible mechanism by which progestins may increase breast cell proliferation in vivo.