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Corticotropin-releasing hormone interacts with interleukin-1 to regulate prostaglandin H synthase-2 expression in human myometrium during pregnancy and labor
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Markovic, Danijela, Bari, Muhammad F., Lu, B., Vatish, Manu and Grammatopoulos, Dimitris (2013) Corticotropin-releasing hormone interacts with interleukin-1 to regulate prostaglandin H synthase-2 expression in human myometrium during pregnancy and labor. Journal of Clinical Endocrinology & Metabolism, Volume 98 (Number 7). pp. 2864-2875. doi:10.1210/jc.2013-1094 ISSN 0021-972X.
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Official URL: http://dx.doi.org/10.1210/jc.2013-1094
Abstract
Context: The onset of labor appears to involve the activation of myometrial inflammatory pathways, and transcription factors such as nuclear factor-κB (NF-κB) control expression of the contraction-associated proteins required to induce a procontractile phenotype. These responses might involve CRH, which integrates immune and neuroendocrine systems.
Objectives: In human myometrium we investigated cyclooxygenase 2 (PGHS2) expression and regulation by CRH and the proinflammatory cytokine IL-1β before and after labor.
Design: Myometrial tissues obtained from pregnant women at term before (n = 12) or during labor (n = 10) and pathological cases of choriamnionitis-associated term labor (n = 5) were used to isolate primary myocytes and investigate in vitro, CRH effects on basal and IL-1β regulated p65 activation and PGHS2 expression.
Results: In nonlaboring myometrial cells, CRH was unable to induce NF-κB nuclear translocation; however, it altered the temporal dynamics of IL-1β-driven NF-κB nuclear entry by initially delaying entry and subsequently prolonging retention. These CRH-R1-driven effects were associated with a modest inhibitory action in the early phase (within 2 hours) of IL-1β stimulated PGHS2 mRNA expression, whereas prolonged stimulation for 6–18 hours augmented the IL-1β effects. The early-phase effect required intact protein kinase A activity and was diminished after the onset of labor. The presence of chorioamnionitis led to exaggerated PGHS2 mRNA responses to IL-1β but diminished effects of CRH.
Conclusions: CRH is involved in the inflammatory regulation of PGHS2 expression before and during labor; these actions might be important in priming and preparing the myometrium for labor and cellular adaptive responses to inflammatory mediators
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RG Gynecology and obstetrics |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Corticotropin releasing hormone, Interleukin-1, Prostaglandins, Myometrium, Labor (Obstetrics) -- Endocrine aspects | ||||
Journal or Publication Title: | Journal of Clinical Endocrinology & Metabolism | ||||
Publisher: | The Endocrine Society | ||||
ISSN: | 0021-972X | ||||
Official Date: | 1 July 2013 | ||||
Dates: |
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Volume: | Volume 98 | ||||
Number: | Number 7 | ||||
Page Range: | pp. 2864-2875 | ||||
DOI: | 10.1210/jc.2013-1094 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Date of first compliant deposit: | 25 December 2015 | ||||
Date of first compliant Open Access: | 25 December 2015 | ||||
Funder: | Wellcome Trust (London, England), Science City Research Alliance |
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