Aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 may enhance progesterone metabolism in ovarian endometriosis
Aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 may enhance progesterone metabolism in ovarian endometriosis
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DOI：
10.1016/j.cbi.2011.01.003
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发表时间：
2011-05-30
影响因子：
5.1
通讯作者：
Rizner, Lanisnik
中科院分区：
文献类型：
--
作者：
Hevir, N.;Vouk, K.;Rizner, Lanisnik
子宫内膜异位症是一种非常常见的疾病，其特征是雌二醇形成增加和黄体酮作用紊乱。后者通常被解释为缺乏孕激素受体B （PR-B）表达，而孕激素受体前代谢的作用尚不完全清楚。在正常子宫内膜中，孕酮被还原性20 α -羟基类固醇脱氢酶（20 α - hsds）、3 α / β - hsds和5 α / β -还原酶代谢。醛酮还原酶1C1和1C3 （AKR1C1和AKR1C3）是20 α - hsd的主要还原酶，而氧化反应由17 β - hsd 2型（HSD17B2）催化。此外，3个α - hsd和3个β - hsd活性与AKR1C同工酶有关。此外，5 α -还原酶1型和2型（SRD5A1, SRD5A2）和5 β -还原酶（AKR1D1）负责5 α -和5 β -还原妊娠的形成。本研究检测了31例卵巢子宫内膜异位症和28例正常子宫内膜中PR-AB和孕酮代谢酶的表达。Real-time PCR分析显示PR-AB、HSD17B2和SRD5A2 mRNA水平显著降低，AKR1C1、AKR1C2、AKR1C3和SRD5A1 mRNA水平显著升高，AKR1D1 mRNA水平可忽略。免疫组化染色显示上皮细胞PR-B水平明显低于对照，基质细胞PR-B水平无显著差异，AKR1C3表达无显著差异，AKR1C2水平仅在基质细胞中显著升高。因此，我们在mRNA水平和部分细胞水平上的表达分析数据表明，SRD5A1增强了孕酮的代谢，AKR1C1、AKR1C2和AKR1C3的20 α - hsd和3 α / β - hsd活性增强。2011爱思唯尔爱尔兰有限公司版权所有。
Endometriosis is a very common disease that is characterized by increased formation of estradiol and disturbed progesterone action. This latter is usually explained by a lack of progesterone receptor B (PR-B) expression, while the role of pre-receptor metabolism of progesterone is not yet fully understood. In normal endometrium, progesterone is metabolized by reductive 20 alpha-hydroxysteroid dehydrogenases (20 alpha-HSDs), 3 alpha/beta-HSDs and 5 alpha/beta-reductases. The aldo-keto reductases 1C1 and 1C3 (AKR1C1 and AKR1C3) are the major reductive 20 alpha-HSDs, while the oxidative reaction is catalyzed by 17 beta-HSD type 2 (HSD17B2). Also, 3 alpha-HSD and 3 beta-HSD activities have been associated with the AKR1C isozymes. Additionally, 5 alpha-reductase types 1 and 2 (SRD5A1, SRD5A2) and 5 beta-reductase (AKR1D1) are responsible for the formation of 5 alpha- and 5 beta-reduced pregnanes. In this study, we examined the expression of PR-AB and the progesterone metabolizing enzymes in 31 specimens of ovarian endometriosis and 28 specimens of normal endometrium. Real-time PCR analysis revealed significantly decreased mRNA levels of PR-AB, HSD17B2 and SRD5A2, significantly increased mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1, and negligible mRNA levels of AKR1D1. Immunohistochemistry staining of endometriotic tissue compared to control endometrium showed significantly lower PR-B levels in epithelial cells and no significant differences in stromal cells, there were no significant differences in the expression of AKR1C3 and significantly higher AKR1C2 levels were seen only in stromal cells. Our expression analysis data at the mRNA level and partially at the cellular level thus suggest enhanced metabolism of progesterone by SRD5A1 and the 20 alpha-HSD and 3 alpha/beta-HSD activities of AKR1C1, AKR1C2 and AKR1C3. (C) 2011 Elsevier Ireland Ltd. All rights reserved.