Expression of human aldo-keto reductase 1C2 in cell lines of peritoneal endometriosis: Potential implications in metabolism of progesterone and dydrogesterone and inhibition by progestins

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• 作者：Nata&scaron ; a Berani膷^a ; Petra Bro啪i膷^a ; Boris Brus^b ; Izidor Sosi膷^b ; Stanislav Gobec^b ; Tea Lani&scaron ; nik Ri啪ner^a ; ^{Tea.Lanisnik-Rizner@mf.uni-lj.si}
• 关键词：5伪-DHT ; 5伪-dihydrotestosterone ; 5伪-DHP ; 5伪-dihydroprogesterone
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2012
• 期刊代码：172_09600760
• 类别：med
• 出版时间：May, 2012
• 卷：130
• 期：1-2
• 页码：16-25
• 文件大小：933 K

摘要

The human aldo-keto reductase AKR1C2 converts 5伪-dihydrotestosterone to the less active 3伪-androstanediol and has a minor 20-ketosteroid reductase activity that metabolises progesterone to 20伪-hydroxyprogesterone. AKR1C2 is expressed in different peripheral tissues, but its role in uterine diseases like endometriosis has not been studied in detail. Some progestins used for treatment of endometriosis inhibit AKR1C1 and AKR1C3, with unknown effects on AKR1C2. In this study we investigated expression of AKR1C2 in the model cell lines of peritoneal endometriosis, and examined the ability of recombinant AKR1C2 to metabolise progesterone and progestin dydrogesterone, as well as its potential inhibition by progestins. AKR1C2 is expressed in epithelial and stromal endometriotic cell lines at the mRNA level. The recombinant enzyme catalyses reduction of progesterone to 20伪-hydroxyprogesterone with a 10-fold lower catalytic efficiency than the major 20-ketosteroid reductase, AKR1C1. AKR1C2 also metabolises progestin dydrogesterone to its 20伪-dihydrodydrogesterone, with 8.6-fold higher catalytic efficiency than 5伪-dihydrotestosterone. Among the progestins that are currently used for treatment of endometriosis, dydrogesterone, medroxyprogesterone acetate and 20伪-dihydrodydrogesterone act as AKR1C2 inhibitors with low 渭M K_i values in vitro. Their potential in vivo effects should be further studied.