DOWN-REGULATION OF ANDROGEN RECEPTOR BY PROGESTINS AND INTERFERENCE WITH ESTROGENIC OR ANDROGENIC STIMULATION OF MAMMARY-CARCINOMA CELL-GROWTH

The regulatory influence of medroxyprogesterone acetate (MPA) on estrogen and androgen receptors of the human breast cancer cell lines MCF-7 and EFM-19 was explored in conjunction with the growth-promoting properties of these steroids. In the absence of steroidal stimulation, up to 1 μM MPA had no effect on the proliferation of the MCF-7 cell strain used and of EFM-19 cells. Under stimulation with 10 nM 17 β-estradiol or 1 μM dihydrotestosterone, dose-dependent inhibition of the cell proliferation rates by 0.1-1 μM MPA was observed. Binding of MPA to the androgen receptor (Kd=2.1 nM) but not to the estrogen receptor was demonstrable. During incubation of MCF-7 or EFM-19 cells with 1 μM MPA for 7 days, the estrogen and androgen receptor contents were down-regulated by approximately 50% and 60%, respectively. Likewise, the number of androgen-binding sites was reduced to 35% of the untreated controls after incubation of MCF-7 cells with 1 μM synthetic progestin R5020 for 7 days. The results indicate down-regulation of estrogen and androgen receptors by progestins in the absence of stimulatory effects on the proliferation of mammary carcinoma cells. © 1990 Springer-Verlag.