Induction of PGF2α synthesis by cortisol through GR dependent induction of CBR1 in human amnion fibroblasts

Chunming Guo, Wangsheng Wang, Chao Liu, Leslie Myatt, Kang Sun

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Abundant evidence indicates a pivotal role of prostaglandin F2α (PGF2α) in human parturition. Both the fetal and maternal sides of the fetal membranes synthesize PGF2α. In addition to the synthesis of PGF2α from PGH2 by PGF synthase (PGFS), PGF2α can also be converted from PGE2 by carbonyl reductase 1 (CBR1). Here, we showed that there was concurrent increased production of cortisol and PGF2α 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 (0.01-1μM) increased PGF2α 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 immu-noprecipitation (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 PGF2α production in human amnion fibroblasts. In conclusion, CBR1 may play a critical role in PGF2α synthesis in human amnion fibroblasts, and cortisol promotes the conversion of PGE2 into PGF2α 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 PGF2α in human amnion tissue with labor, and these findings may account for the increased production of PGF2α in the fetal membranes prior to the onset of labor.

Original languageEnglish (US)
Pages (from-to)3017-3024
Number of pages8
JournalEndocrinology
Volume155
Issue number8
DOIs
StatePublished - 2014
Externally publishedYes

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Amnion
Dinoprost
Alcohol Oxidoreductases
Glucocorticoid Receptors
Hydrocortisone
Fibroblasts
Extraembryonic Membranes
prostaglandin-F synthase
Dinoprostone
Small Interfering RNA
human CBR1 protein
Prostaglandin H2
Labor Onset
Rutin
RNA Polymerase II
Chromatin
Mothers
Parturition

ASJC Scopus subject areas

  • Endocrinology

Cite this

Induction of PGF2α synthesis by cortisol through GR dependent induction of CBR1 in human amnion fibroblasts. / Guo, Chunming; Wang, Wangsheng; Liu, Chao; Myatt, Leslie; Sun, Kang.

In: Endocrinology, Vol. 155, No. 8, 2014, p. 3017-3024.

Research output: Contribution to journalArticle

Guo, Chunming ; Wang, Wangsheng ; Liu, Chao ; Myatt, Leslie ; Sun, Kang. / Induction of PGF2α synthesis by cortisol through GR dependent induction of CBR1 in human amnion fibroblasts. In: Endocrinology. 2014 ; Vol. 155, No. 8. pp. 3017-3024.
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AB - Abundant evidence indicates a pivotal role of prostaglandin F2α (PGF2α) in human parturition. Both the fetal and maternal sides of the fetal membranes synthesize PGF2α. In addition to the synthesis of PGF2α from PGH2 by PGF synthase (PGFS), PGF2α can also be converted from PGE2 by carbonyl reductase 1 (CBR1). Here, we showed that there was concurrent increased production of cortisol and PGF2α 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 (0.01-1μM) increased PGF2α 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 immu-noprecipitation (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 PGF2α production in human amnion fibroblasts. In conclusion, CBR1 may play a critical role in PGF2α synthesis in human amnion fibroblasts, and cortisol promotes the conversion of PGE2 into PGF2α 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 PGF2α in human amnion tissue with labor, and these findings may account for the increased production of PGF2α in the fetal membranes prior to the onset of labor.

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