Department of Obstetrics and Gynecology, Clinic for Endocrinology and Reproductive Medicine, University of Freiburg, Freiburg, Germany.
Fertil Steril. 2012 Oct;98(4):1017-22. doi: 10.1016/j.fertnstert.2012.06.010. Epub 2012 Jul 4.
To elucidate the mode of action of chlormadinone acetate (CMA) in reducing dysmenorrheic pain by studying the effects of CMA and dexamethasone (DEX) on messenger RNA (mRNA) abundance of cyclo-oxygenase-2 (COX-2), annexin-1 (ANXA1), glucocorticoid receptor (GR), progesterone receptor (PR), and concentrations of prostaglandin F(2α) (PGF(2α)) and leukotrienes B(4) (LTB(4)) and C(4) (LTC(4)) in human endometrial explants.
Ex vivo study.
University hospital.
PATIENT(S): Fifteen premenopausal patients undergoing surgery for benign gynecologic disorders.
INTERVENTION(S): Endometrial explants were obtained by aspiration curettage and stimulated ex vivo with interleukin-1β before exposure to CMA or DEX; mRNA levels were determined via reverse transcription-quantitative real-time polymerase chain reaction, and concentrations of arachidonic acid metabolites by enzyme immunoassays.
MAIN OUTCOME MEASURE(S): Messenger RNA levels of COX-2, ANXA1, PR, and GR; concentrations of PGF(2α), LTB(4), and LTC(4) in endometrial explants treated with CMA or DEX.
RESULT(S): In IL-1β-treated explants COX-2 mRNA and PGF(2α), concentrations were significantly down-regulated by CMA but not by DEX. Chlormadinone acetate did not affect mRNA abundance of ANXA1, PR, and GR.
CONCLUSION(S): Our data suggest that CMA is a suppressor of COX-2 expression. Comparison with DEX revealed that progestin-specific activity of CMA may mainly be responsible for suppression of prostaglandin biosynthesis in human endometrium.
通过研究氯地孕酮（CMA）和地塞米松（DEX）对环氧化酶-2（COX-2）、膜联蛋白-1（ANXA1）、糖皮质激素受体（GR）、孕激素受体（PR）信使 RNA（mRNA）丰度以及前列腺素 F（2α）（PGF（2α））、白三烯 B（4）（LTB（4））和 C（4）（LTC（4））浓度的影响，阐明 CMA 减轻痛经疼痛的作用机制。
离体研究。
大学医院。
15 名因良性妇科疾病接受手术的绝经前患者。
通过宫腔吸引刮宫术获取子宫内膜标本，并用白细胞介素-1β刺激离体后暴露于 CMA 或 DEX；通过逆转录定量实时聚合酶链反应测定 mRNA 水平，通过酶免疫分析法测定花生四烯酸代谢物的浓度。
COX-2、ANXA1、PR 和 GR 的 mRNA 水平；用 CMA 或 DEX 处理的子宫内膜标本中 PGF（2α）、LTB（4）和 LTC（4）的浓度。
在白细胞介素-1β处理的标本中，CMA 显著下调 COX-2 mRNA 和 PGF（2α）的表达，但 DEX 无此作用。CMA 不影响 ANXA1、PR 和 GR 的 mRNA 丰度。
我们的数据表明 CMA 是 COX-2 表达的抑制剂。与 DEX 的比较表明，CMA 的孕激素特异性活性可能主要负责抑制人子宫内膜中前列腺素的生物合成。
