Steroidal regulation of oestradiol-17 beta dehydrogenase activity of the human breast cancer cell line MCF-7.

We have examined the direct effects of progestins, oestrogens, peptide hormones and growth factors on oestradiol-17 beta dehydrogenase (OE2DH) activity of cultures of the human breast cancer cell line MCF-7. Cells were cultured in the presence of steroid or peptide for 6 days, after which the number of cells was determined and cellular OE2DH activity assessed. Progesterone, 6 alpha-methyl-17 alpha-hydroxyprogesterone acetate, norethisterone and D(-)-norgestrel all profoundly inhibited cell mitosis and stimulated reductive (oestrone----oestradiol-17 beta) and oxidative (oestradiol-17 beta----oestrone) OE2DH activity. Both oestrone and oestradiol-17 beta directly stimulated reductive OE2DH activity, but had no effect on the oxidative direction. Oestradiol-17 beta stimulated cell growth only in phenol-red free culture medium. Ovine prolactin, LH, epidermal growth factor and transforming growth factor did not alter OE2DH activity but small stimulatory effects on the growth of MCF-7 cells were exerted by prolactin and a combination of transforming growth factor with epidermal growth factor. It is concluded that these results may explain, at least in part, the alterations in mitotic activity and tissue oestradiol-17 beta levels observed in breast tissue during varying physiological and pathological conditions, such as during the menstrual cycle and in breast cancers.