title: 5 Beta-dihydroprogesterone and steroid 5 beta-reductase decrease in association with human parturition at term.
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 5beta-dihydroprogesterone (5betaDHP) has been shown to be a potent tocolytic in vitro. We quantified plasma concentrations of 5betaDHP in association with the onset of spontaneous labour in women at term and steroid 5beta-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 5betaDHP were separated by high-performance liquid chromatography (HPLC) and then quantified by radioimmunoassay (RIA). 5betaDHP concentration decreased two-fold (P = 0.00001, n = 25) from 0.317 +/- 0.039 nmol/ml to 0.178 +/- 0.017 nmol/ml in association with active labour. Tissue 5beta-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 5betaDHP in the onset of spontaneous human labour. Further studies exploring this hitherto unrecognized endocrinological pathway are indicated.
authors.affiliation: Pregnancy Research Centre and University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Carlton, Victoria, Australia. penny.sheehan@rwh.org.au
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Sheehan
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Rice
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
mesh_terms: D043582:5-alpha-Dihydroprogesterone / Q000097:blood / Q000378:metabolism*; D000650:Amnion / Q000201:enzymology; D002823:Chorion / Q000201:enzymology; D005260:Female; D006801:Humans; D007743:Labor, Obstetric / Q000378:metabolism*; D009215:Myometrium / Q000201:enzymology; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D036801:Parturition / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D043582:5-alpha-Dihydroprogesterone; D010088:Oxidoreductases; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase