5β-Dihydroprogesterone and steroid 5β-reductase decrease in association with human parturition at term

Penelope M. Sheehan, Gregory E. Rice, Eric K. Moses, Shaun P. Brennecke

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    Abstract

    The role of progesterone withdrawal in human parturition continues to provoke controversy. One possible mechanism by which functional progesterone withdrawal may be achieved is by a decrease in the circulating concentration of its bioactive metabolites. The progesterone metabolite 5β-dihydroprogesterone (5βDHP) has been shown to be a potent tocolytic in vitro. We quantified plasma concentrations of 5βDHP in association with the onset of spontaneous labour in women at term and steroid 5β-reductase mRNA expression in placenta, myometrium, chorion and amnion in relation to parturition, using real time RT-PCR. Serial blood samples were obtained from patients late in pregnancy, before term labour, during term labour and within the first 24 h postpartum. Following organic solvent extraction, steroids including 5βDHP were separated by high-performance liquid chromatography (HPLC) and then quantified by radioimmunoassay (RIA). 5βDHP concentration decreased two-fold (P = 0.00001, n = 25) from 0.317 ± 0.039 nmol/ml to 0.178 ± 0.017nmol/ml in association with active labour. Tissue 5β-reductase mRNA-relative abundance was determined in placenta, myometrium, chorion and amnion obtained from labouring and non-labouring women. In placenta and myometrium, relative expression decreased significantly in association with labour, by about two-fold and 10-fold, respectively. These data are consistent with a possible role for 5βDHP in the onset of spontaneous human labour. Further studies exploring this hitherto unrecognized endocrinological pathway are indicated.

    Original languageEnglish (US)
    Pages (from-to)495-501
    Number of pages7
    JournalMolecular Human Reproduction
    Volume11
    Issue number7
    DOIs
    Publication statusPublished - Jul 1 2005

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    Keywords

    • 5β-dihydroprogesterone
    • 5β-reductase
    • Human
    • Parturition
    • Progesterone metabolites

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Embryology
    • Molecular Biology
    • Genetics
    • Obstetrics and Gynecology
    • Developmental Biology
    • Cell Biology

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