Beijing Ob/Gyn Hospital, Capital Medical University, Beijing, China.
Gynecol Endocrinol. 2012 Nov;28(11):863-6. doi: 10.3109/09513590.2012.671396. Epub 2012 Apr 12.
Recently the first monophasic contraceptive pill containing estradiol has been developed which is thought to be a milestone in contraception. Nomegestrol acetate (NOM) is the progestogenic component. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in the tissue of breast cancer patients, and can predict a progestogen dependent risk of breast cancer.
MCF-7 cells were transfected with PGRMC1 expression plasmid, and were stimulated with estradiol (E2, 10(-12) and 10(-10) M). NOM, progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) (each 10(-7) M) were added sequentially or continuously.
E2 at 10(-10) M elicited a significant increase of cell proliferation from 150 to 200%. No effect was seen at 10(-12) M. Addition of the progestogens to E2 at 10(-10) M had no significant effect. However, at an E2 10(-12) M, NET significantly stimulated cell proliferation more pronounced in the continuous combined model. No effect was seen for NOM, P and MPA. The E2/NET combined effect could be abrogated by the addition of an estrogen receptor (ER) antagonist.
Since NOM did not increase proliferation it may be concluded that it will be neutral in terms of breast cancer risk when combined with E2 at least in women overexpressing PGRMC1.
最近开发出了第一种含有雌二醇的单相避孕药，被认为是避孕领域的一个里程碑。醋酸诺美孕酮（NOM）是孕激素成分。孕激素受体膜成分 1（PGRMC1）在乳腺癌患者的组织中高度表达，并且可以预测孕激素依赖性乳腺癌的风险。
将 PGRMC1 表达质粒转染 MCF-7 细胞，并分别用雌二醇（E2，10（-12）和 10（-10）M）刺激。然后依次或连续添加 NOM、孕酮（P）、醋酸甲地孕酮（MPA）和炔诺酮（NET）（每种 10（-7）M）。
E2 在 10（-10）M 时引起细胞增殖从 150%增加到 200%，而在 10（-12）M 时没有影响。在 E2 10（-10）M 时，添加孕激素对细胞增殖没有显著影响。然而，在 E2 10（-12）M 时，NET 在连续联合模型中更显著地刺激细胞增殖。NOM、P 和 MPA 均无影响。添加雌激素受体（ER）拮抗剂可消除 E2/NET 的联合作用。
由于 NOM 不会增加增殖，因此可以得出结论，当与 E2 联合使用时，至少在过度表达 PGRMC1 的女性中，它在乳腺癌风险方面可能是中性的。
