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Uterine stretch and progesterone action
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Lei, K., Chen, Li, Ph.D., Cryar, B. J., Hua, R., Sooranna, S. R., Brosens, Jan J., Bennett, P. R. and Johnson, M. R.. (2011) Uterine stretch and progesterone action. Journal of Clinical Endocrinology & Metabolism , Vol.96 (No.6). E1013-E1024. ISSN 0021-972x
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Official URL: http://dx.doi.org/10.1210/jc.2010-2310
Abstract
Context: Progesterone administration reduces the risk of preterm labor in high-risk women with singleton pregnancies but has no effect in women with a multiple pregnancy.
Objective: We investigated whether progesterone is able to inhibit stretch-induced gene expression and/or whether stretch in turn inhibits progesterone action, perhaps providing an explanation for the functional progesterone withdrawal associated with human labor.
Methods and Results: In a series of in vitro studies using primary cultures of human myometrial cells, we found that preincubation with progesterone did not block stretch-induced ERK1/2 activation and cyclooxygenase-2 mRNA expression. Furthermore, we found that stretch did not alter the ability of progesterone to: 1) modulate progesterone-responsive gene expression; 2) activate a luciferase-linked progesterone response element; or 3) repress IL-1β-driven cyclooxygenase-2 mRNA expression. We did find that stretch reduced the expression of progesterone receptor mRNA via nuclear factor κB activation but that this did not alter myometrial progesterone response.
Conclusion: These data show that progesterone does not inhibit stretch-induced MAPK activation or gene expression, possibly explaining why progesterone is ineffective in the prevention of preterm labor in multiple pregnancy. Although stretch did reduce progesterone receptor expression in a nuclear factor κB-dependent manner, this was not sufficient to inhibit progesterone action, suggesting that it is not responsible for the functional progesterone withdrawal observed with the onset of human labor.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > R Medicine (General) | ||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Reproductive Health Faculty of Medicine > Warwick Medical School |
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| Journal or Publication Title: | Journal of Clinical Endocrinology & Metabolism | ||||
| Publisher: | Endocrine Society | ||||
| ISSN: | 0021-972x | ||||
| Official Date: | 1 June 2011 | ||||
| Dates: |
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| Volume: | Vol.96 | ||||
| Number: | No.6 | ||||
| Page Range: | E1013-E1024 | ||||
| Identification Number: | 10.1210/jc.2010-2310 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| URI: | http://wrap.warwick.ac.uk/id/eprint/46587 |
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