Corticotropin-releasing hormone interacts with interleukin-1β to regulate prostaglandin H synthase-2 expression in human myometrium during pregnancy and labor.

Context: The onset of labor appears to involve the activation of myometrial inflammatory pathways, and transcription factors such as nuclear factor-kappa B (NF-kappa B) 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-1 beta 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-1 beta regulated p65 activation and PGHS2 expression. Results: In nonlaboring myometrial cells, CRH was unable to induce NF-kappa B nuclear translocation; however, it altered the temporal dynamics of IL-1 beta-driven NF-kappa B 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-1 beta stimulated PGHS2 mRNA expression, whereas prolonged stimulation for 6-18 hours augmented the IL-1 beta 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-1 beta 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.