American journal of obstetrics and gynecology · 2005
Metabolites of progesterone and the pregnane X receptor: a novel pathway regulating uterine contractility in pregnancy?
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Mitchell Bryan F, Mitchell Jana M, Chowdhury Jeeshan, Tougas Michelle, Engelen Sanne M E, Senff Nancy, Heijnen Iris, Moore John T, Goodwin Bryan, Wong Susan, Davidge Sandra T
Аннотация
OBJECTIVE: The purpose of this study was to determine the role of 5beta-dihydroprogesterone (5beta-DHP), acting through the nuclear receptor pregnane X receptor (PXR), in regulating uterine contractility.
STUDY DESIGN: Uterine contractility was studied in tissues from women, rats, and mice. Messenger RNA was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR), and protein was measured using enzyme assays, immunofluorescence microscopy, and Western analyses.
RESULTS: Human and rat uterine tissues contain mRNA and protein for 5beta-reductase and for PXR. Acute in vitro treatment with 5beta-DHP causes rapid uterine relaxation that is not mediated by PXR. Chronic in vivo administration of 5beta-DHP to mice with intact PXR, but not in mice with disrupted PXR, causes an increased effect of 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). This suggests that 5beta-DHP increased iNOS-modulated uterine tone, as occurs during pregnancy.
CONCLUSION: These data support the hypothesis that metabolites of progesterone may act chronically through a PXR-mediated mechanism to regulate uterine contractility.
STUDY DESIGN: Uterine contractility was studied in tissues from women, rats, and mice. Messenger RNA was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR), and protein was measured using enzyme assays, immunofluorescence microscopy, and Western analyses.
RESULTS: Human and rat uterine tissues contain mRNA and protein for 5beta-reductase and for PXR. Acute in vitro treatment with 5beta-DHP causes rapid uterine relaxation that is not mediated by PXR. Chronic in vivo administration of 5beta-DHP to mice with intact PXR, but not in mice with disrupted PXR, causes an increased effect of 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). This suggests that 5beta-DHP increased iNOS-modulated uterine tone, as occurs during pregnancy.
CONCLUSION: These data support the hypothesis that metabolites of progesterone may act chronically through a PXR-mediated mechanism to regulate uterine contractility.
Предметные рубрики MeSH
Analysis of VarianceAnimalsBase SequenceBlotting, WesternEnzyme-Linked Immunosorbent AssayFemaleHumansMiceMice, KnockoutMicroscopy, FluorescenceModels, AnimalMolecular Sequence DataMyometriumOrgan Culture TechniquesPregnancyPregnancy, AnimalPregnane X ReceptorProbabilityProgesteroneRNA, MessengerRatsRats, Sprague-DawleyReceptors, Cytoplasmic and NuclearReceptors, SteroidReverse Transcriptase Polymerase Chain ReactionSpecies SpecificityUp-RegulationUterine Contraction