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Cyclic AMP enhances progesterone action in human myometrial cells

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Chen, Li, Lei, Kaiyu, Malawana, Johann, Yulia, Angela, Sooranna, Suren R., Bennett, Phillip R., Liang, Zhiqing, Grammatopoulos, Dimitris and Johnson, Mark R. (2014) Cyclic AMP enhances progesterone action in human myometrial cells. Molecular and Cellular Endocrinology, Volume 382 (Number 1). pp. 334-343. doi:10.1016/j.mce.2013.10.018

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Official URL: http://dx.doi.org/10.1016/j.mce.2013.10.018

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Abstract

Cyclic AMP (cAMP) has been shown to promote progesterone and glucocorticoid action in a variety of cellular settings. In this study, we have used human myometrial cells to investigate whether cAMP potentiates the ability of progesterone to repress IL-1β-driven COX-2 expression. We found that forskolin enhanced progesterone-repression of IL-1β-driven COX-2 expression in association with delayed IL-1β-induced nuclear phospho-p65 entry and reduced NF-κB binding to the COX-2 promoter. Further, forskolin enhanced the progesterone-induced expression of FKBP5 and 11βHSD1, progesterone-driven activity of a progesterone response element (PRE) and progesterone receptor (PR)-B binding to a transfected PRE. In addition, forskolin treatment increased PR-B levels and reduced the PR-A:PR-B ratio while acutely decreasing the association between PR and nuclear receptor co-repressor (NCoR) and reducing NCoR levels after 6 h. These findings are of importance in situations where enhancing progesterone activity is desirable, for example in the management of endometrial cancer, the promotion of endometrial receptivity or the maintenance of myometrial quiescence during pregnancy

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Molecular and Cellular Endocrinology
Publisher: Elsevier
ISSN: 0303-7207
Official Date: 25 January 2014
Dates:
DateEvent
25 January 2014Published
24 October 2013Available
17 October 2013Accepted
14 October 2013Submitted
Volume: Volume 382
Number: Number 1
Page Range: pp. 334-343
DOI: 10.1016/j.mce.2013.10.018
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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