Author/Editor     Beranič, Nataša; Brožič, Petra; Brus, Boris; Sosič, Izidor; Gobec, Stanislav; Lanišnik-Rižner, Tea
Title     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
Type     članek
Source     J Steroid Biochem Mol Biol
Vol. and No.     Letnik 130, št. 1-2
Publication year     2012
Volume     str. 16-25
Language     eng
Abstract     The human aldo-keto reductase AKR1C2 converts 5alpha-dihydrotestosterone to the less active 3alpha-androstanediol and has a minor 20-ketosteroid reductase activity that metabolises progesterone to 20alpha-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 20alpha-hydroxyprogesterone with a 10-fold lower catalytic efficiency than the major 20-ketosteroid reductase, AKR1C1. AKR1C2 also metabolises progestin dydrogesterone to its 20alpha-dihydrodydrogesterone, with 8.6-fold higher catalytic efficiency than 5alpha-dihydrotestosterone. Among the progestins that are currently used for treatment of endometriosis, dydrogesterone, medroxyprogesterone acetate and 20alpha-dihydrodydrogesterone act as AKR1C2 inhibitors with low muM K(i) values in vitro. Their potential in vivo effects should be further studied.
Descriptors     ENDOMETRIOSIS
PERITONEAL DIALYSIS
PROGESTERONE
OXIDOREDUCTASES
DYDROGESTERONE
20-HYDROXYSTEROID DEHYDROGENASES
MEDROXYPROGESTERONE 17-ACETATE
POLYMERASE CHAIN REACTION
CELLS, CULTURED
NUCLEAR MAGNETIC RESONANCE
ESCHERICHIA COLI
TRANSFECTION
RECOMBINANT PROTEINS