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

Beranič N, Nataša Beranič, Petra Brožič, Brožič P, Boris Brus, Brus B, Izidor Sosič, Stanislav Gobec, Tea Lanišnik Rižner
The Journal of steroid biochemistry and molecular biology · 2012 · vol. 130(1-2) , pp. 16–25 · doi:10.1016/j.jsbmb.2011.12.011 · PMID:22245609 · W2005680774
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This study investigated the expression of human aldo-keto reductase 1C2 in peritoneal endometriosis cell lines, finding its potential involvement in progesterone and dydrogesterone metabolism and inhibition by progestins.

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Abstract

The human aldo-keto reductase AKR1C2 converts 5α-dihydrotestosterone to the less active 3α-androstanediol and has a minor 20-ketosteroid reductase activity that metabolises progesterone to 20α-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 20α-hydroxyprogesterone with a 10-fold lower catalytic efficiency than the major 20-ketosteroid reductase, AKR1C1. AKR1C2 also metabolises progestin dydrogesterone to its 20α-dihydrodydrogesterone, with 8.6-fold higher catalytic efficiency than 5α-dihydrotestosterone. Among the progestins that are currently used for treatment of endometriosis, dydrogesterone, medroxyprogesterone acetate and 20α-dihydrodydrogesterone act as AKR1C2 inhibitors with low μM K(i) values in vitro. Their potential in vivo effects should be further studied.

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Condition tags

endometriosis

MeSH descriptors

Dydrogesterone Endometriosis Hydroxysteroid Dehydrogenases Hydroxysteroid Dehydrogenases Peritoneum Progesterone Progestins 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) Catalytic Domain Catalytic Domain Cell Line Cell Line Dihydrotestosterone Dihydrotestosterone Dihydrotestosterone Dydrogesterone Dydrogesterone Dydrogesterone Endometriosis

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (38)

Cited by (2)

SciLite annotations

organisms 2
human human
chemicals 17
progesterone dydrogesterone progestin progesterone progestin progesterone progestin dydrogesterone progestin progesterone medroxyprogesterone delta(1)-dihydrotestosterone progestin dydrogesterone medroxyprogesterone acetate dydrogesterone

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