Summary
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 17β-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 (K d=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.
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Abbreviations
- MPA:
-
medroxyprogesterone acetate
- R1881:
-
methyltrienolone-17β-hydroxy-17α-methylestra-4,9,11-triene-3-one
- R5020:
-
17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione
- PBS:
-
phosphate-buffered saline
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Dedicated to Prof. Dr. med. Rolf Kaiser, Director Emeritus of the Department of Obstetrics and Gynecology of the University of Cologne, on the occasion of his 70th birthday
Supported by the “Landesversicherungsanstalt Hessen”, Frankfurt.
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Hackenberg, R., Hofmann, J., Wolff, G. et al. Down-regulation of androgen receptor by progestins and interference with estrogenic or androgenic stimulation of mammary carcinoma cell growth. J Cancer Res Clin Oncol 116, 492–498 (1990). https://doi.org/10.1007/BF01613000
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DOI: https://doi.org/10.1007/BF01613000