Aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 may enhance progesterone metabolism in ovarian endometriosis

作者：Hevir N; Vouk K; Sinkovec J; Ribic Pucelj M; Rizner Lanisnik^*

来源：Chemico-Biological Interactions, 2011, 191(1-3): 217-226.

DOI：10.1016/j.cbi.2011.01.003

• 5 alpha-Dihydroprogesterone
• 20 alpha-Hydroxyprogesterone
• 5 alpha-Reductase (SRD5A)
• 5 beta-Reductase (AKR1D1)
• Progesterone receptor B (PR-B)

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.

• 出版日期2011-5-30