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  • Title: Metabolites of progesterone and the pregnane X receptor: a novel pathway regulating uterine contractility in pregnancy?
    Author: Mitchell BF, Mitchell JM, Chowdhury J, Tougas M, Engelen SM, Senff N, Heijnen I, Moore JT, Goodwin B, Wong S, Davidge ST.
    Journal: Am J Obstet Gynecol; 2005 Apr; 192(4):1304-13; discussion 1313-5. PubMed ID: 15846226.
    Abstract:
    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.
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