Basal and interleukin-1beta-stimulated prostaglandin production from cultured human myometrial cells: differential regulation by corticotropin-releasing hormone.
During pregnancy, placental CRH acts on human myometrium via specific receptors and might play a role in the regulation of myometrial contractility and hence human parturition. The myometrium is the site of production and target of several PGs, which can be activated by cytokines, especially during infection-induced preterm labor. We established primary human myometrial cell cultures that express functional CRH receptors (CRH-R1alpha, -R1beta, -Rlc, and -R2beta) to investigate the possible regulation of PG production by CRH. We studied the effect of CRH on the two major myometrial PGs, PGE2 and 6-keto PGF1alpha. Human CRH was able to partially inhibit basal, interleukin-1beta-stimulated, and oxytocin-stimulated PGE2 production (56 +/- 11%, 45 +/- 8%, and 58 +/- 6% inhibition, respectively). This effect was blocked by a specific CRH receptor antagonist in a concentration-dependent manner. Furthermore, CRH had no effect on 6-keto PGF1alpha production, indicating that the CRH inhibitory action does not involve suppression of cyclooxygenase, the enzyme responsible for the production of both PGE2 and 6-keto-PGF1alpha. These data further support the view that during pregnancy, CRH may promote myometrial quiescence and might play an important role in the regulation of human labor.
Grammatopoulos
D K
DK
Sir Quinton Hazell Molecular Medicine Research Center, Department of Biological Sciences, University of Warwick, Coventry, United Kingdom. chdg@dna.bio.warwick.ac.uk
Hillhouse
E W
EW
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical
D007375:Interleukin-1; D011453:Prostaglandins; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D010121:Oxytocin; D015121:6-Ketoprostaglandin F1 alpha; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D015232:Dinoprostone