Induction of PGF2? synthesis by cortisol through GR dependent induction of CBR1 in human amnion fibroblasts.

ABSTRACT: Abundant evidence indicates a pivotal role of prostaglandin F2? (PGF2?) in human parturition. Both the fetal and maternal sides of the fetal membranes synthesize PGF2?. In addition to the synthesis of PGF2? from PGH2 by PGF synthase (PGFS), PGF2? can also be converted from PGE2 by carbonyl reductase 1 (CBR1). Here, we showed that there was concurrent increased production of cortisol and PGF2? in association with the elevation of CBR1 in human amnion obtained at term with labor versus term without labor. In cultured primary human amnion fibroblasts, cortisol (0.01-1?M) increased PGF2? production in a concentration-dependent manner, in parallel with elevation of CBR1 levels. Either siRNA-mediated knockdown of glucocorticoid receptor (GR) expression or GR antagonist RU486 attenuated the induction of CBR1 by cortisol. Chromatin immunoprecipitation (ChIP) showed an increased enrichment of both GR and RNA polymerase II to CBR1 promoter. Knockdown of CBR1 expression with siRNA or inhibition of CBR1 activity with rutin decreased both basal and cortisol-stimulated PGF2? production in human amnion fibroblasts. In conclusion, CBR1 may play a critical role in PGF2? synthesis in human amnion fibroblasts, and cortisol promotes the conversion of PGE2 into PGF2? via GR-mediated induction of CBR1 in human amnion fibroblasts. This stimulatory effect of cortisol on CBR1 expression may partly explain the concurrent increases of cortisol and PGF2? in human amnion tissue with labor, and these findings may account for the increased production of PGF2? in the fetal membranes prior to the onset of labor.

SUBMITTER: Guo C 

PROVIDER: S-EPMC4098009 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature