title: Down-regulation of androgen receptor by progestins and interference with estrogenic or androgenic stimulation of mammary carcinoma cell growth.
abstract: 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 microM 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 beta-estradiol or 1 microM dihydrotestosterone, dose-dependent inhibition of the cell proliferation rates by 0.1-1 microM 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 microM 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 microM 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.
authors.affiliation: Department of Obstetrics and Gynecology, Philipps University, Marburg, Federal Republic of Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hackenberg
authors.forename: J
authors.initials: J
authors.lastname: Hofmann
authors.forename: G
authors.initials: G
authors.lastname: Wolff
authors.forename: F
authors.initials: F
authors.lastname: Hölzel
authors.forename: K D
authors.initials: KD
authors.lastname: Schulz
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D013196:Dihydrotestosterone / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008525:Medroxyprogesterone / Q000494:pharmacology*; D015741:Metribolone / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000096:biosynthesis
chemical_list: D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D015741:Metribolone; D004958:Estradiol; D008525:Medroxyprogesterone