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Mol. Hum. Reprod. Advance Access published online on July 28, 2005
Molecular Human Reproduction, doi:10.1093/molehr/gah201
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received June 2, 2005
Accepted June 7, 2005

Article

5{beta}-Dihydroprogesterone and steroid 5{beta}--reductase decrease in association with human parturition at term

Penelope M. Sheehan 1*, Gregory E. Rice 2, Eric K. Moses 1, and Shaun P. Brennecke 1

1 Pregnancy Research Centre and University of Melbourne Department of Obstetrics and Gynaecology, Royal Women’s Hospital, Carlton
2 Mercy Perinatal Research Centre, Mercy Hospital for Women, East Melbourne, Victoria, Australia

* To whom correspondence should be addressed.
Penelope M. Sheehan, E-mail: penny.sheehan{at}rwh.org.au


  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 5{beta}-dihydroprogesterone (5{beta}DHP) has been shown to be a potent tocolytic in vitro. We quantified plasma concentrations of 5{beta}DHP in association with the onset of spontaneous labour in women at term and steroid 5{beta}-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 5{beta}DHP were separated by high-performance liquid chromatography (HPLC) and then quantified by radioimmunoassay (RIA). 5{beta}DHP 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 5{beta}-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 5{beta}DHP in the onset of spontaneous human labour. Further studies exploring this hitherto unrecognized endocrinological pathway are indicated.

Keywords: 5{beta}-dihydroprogesterone/5{beta}-reductase/human/parturition/progesterone metabolites.
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