Hackenberg R, Hofmann J, Wolff G, Hölzel F, Schulz K D
Department of Obstetrics and Gynecology, Philipps University, Marburg, Federal Republic of Germany.
J Cancer Res Clin Oncol. 1990;116(5):492-8. doi: 10.1007/BF01613000.
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.
结合这些甾体激素的促生长特性，研究了醋酸甲羟孕酮（MPA）对人乳腺癌细胞系MCF - 7和EFM - 19雌激素和雄激素受体的调节作用。在无甾体激素刺激的情况下，高达1微摩尔的MPA对所用的MCF - 7细胞株和EFM - 19细胞的增殖无影响。在用10纳摩尔17β - 雌二醇或1微摩尔双氢睾酮刺激时，观察到0.1 - 1微摩尔的MPA对细胞增殖速率有剂量依赖性抑制作用。MPA可与雄激素受体结合（解离常数Kd = 2.1纳摩尔），但不与雌激素受体结合。在MCF - 7或EFM - 19细胞与1微摩尔MPA孵育7天期间，雌激素和雄激素受体含量分别下调约50%和60%。同样，在MCF - 7细胞与1微摩尔合成孕激素R5020孵育7天后，雄激素结合位点的数量减少至未处理对照的35%。结果表明，在对乳腺癌细胞增殖无刺激作用的情况下，孕激素可下调雌激素和雄激素受体。
