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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.

Original publication




Journal article


J Clin Endocrinol Metab

Publication Date





2864 - 2875


Adult, Cell Nucleus, Cells, Cultured, Chorioamnionitis, Corticotropin-Releasing Hormone, Cyclooxygenase 2, Female, Gene Expression Regulation, Humans, Interleukin-1beta, Labor, Obstetric, Myometrium, NF-kappa B, Phosphorylation, Pregnancy, Protein Processing, Post-Translational, Protein Transport, RNA, Messenger, Receptors, Corticotropin-Releasing Hormone, Signal Transduction, Tissue Culture Techniques, Transcription Factor RelA