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

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.