Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
Fertil Steril. 2012 Feb;97(2):477-82. doi: 10.1016/j.fertnstert.2011.11.005. Epub 2011 Nov 30.
To determine the effect of dienogest (DNG) on the expression of aromatase and cyclooxygenase-2 (COX-2) and the production of prostaglandin E(2) (PGE(2)) in human endometriotic stromal cells (ESCs).
Experimental study in vitro.
University hospital.
PATIENT(S): Seventeen patients with ovarian endometrioma.
INTERVENTION(S): ESCs from chocolate cyst linings of ovaries were treated with DNG.
MAIN OUTCOME MEASURE(S): Expression of aromatase and COX-2 evaluated in spheroid cultures of human ESCs by real-time quantitative polymerase chain-reaction and immunocytochemistry, production of PGE(2) quantified by enzyme-linked immunosorbent assay (ELISA), and nuclear factor kappa B (NF-κB) DNA-binding examined by ELISA and immunocytochemistry.
RESULT(S): The pharmaceutical actions of DNG on the expression of aromatase and COX-2 and the production of PGE(2) were examined using spheroid cultures of human ESCs. More aromatase, COX-2, and PGE(2) were expressed in spheroid cultures than in conventional ESCs monolayers. In the spheroid cultures, DNG (10(-7) M) and progesterone (10(-7) M) inhibited the expression of aromatase, COX-2, and PGE(2). DNG also inhibited NF-κB DNA-binding activity and reduced the immunocytochemical protein expression of aromatase, COX-2, and NF-κB p50 nuclear localization.
CONCLUSION(S): Because DNG inhibits aromatase and COX-2 expression as well as PGE(2) production in ESCs, these pharmacologic features might contribute to a therapeutic effect of DNG on endometriosis.
探讨地诺孕素（DNG）对人子宫内膜间质细胞（ESCs）芳香化酶和环氧化酶-2（COX-2）表达及前列腺素 E2（PGE2）生成的影响。
体外实验研究。
大学医院。
17 例卵巢子宫内膜异位囊肿患者。
用 DNG 处理卵巢巧克力囊肿内膜来源的 ESCs 球体培养物。
实时定量聚合酶链反应和免疫细胞化学法检测人 ESC 球体培养物中芳香化酶和 COX-2 的表达，酶联免疫吸附测定（ELISA）法检测 PGE2 的生成，ELISA 和免疫细胞化学法检测核因子-κB（NF-κB）DNA 结合。
采用人 ESC 球体培养物研究 DNG 对芳香化酶和 COX-2 表达及 PGE2 生成的药物作用。与常规 ESC 单层培养物相比，ESC 球体培养物中芳香化酶、COX-2 和 PGE2 的表达更高。在 ESC 球体培养物中，DNG（10-7 M）和孕激素（10-7 M）可抑制芳香化酶、COX-2 和 PGE2 的表达。DNG 还可抑制 NF-κB DNA 结合活性，并减少芳香化酶、COX-2 和 NF-κB p50 核定位的免疫细胞化学蛋白表达。
DNG 可抑制 ESCs 中芳香化酶和 COX-2 的表达以及 PGE2 的生成，这些药理作用可能有助于 DNG 治疗子宫内膜异位症。
