5β-Dihydroprogesterone and Human Preterm Labor

Abstract

We previously investigated the progesterone metabolite 5β-dihydroprogesterone (5βDHP) in relation to human parturition at term, demonstrating that peripheral venous concentrations decrease in association with the onset of spontaneous labour. In this study our aim was to determine if 5βDHP concentrations were lower in women presenting in spontaneous preterm labour than in controls matched for gestational age. Blood samples were obtained from women presenting in spontaneous preterm labour (n = 20). The diagnosis was made on the presence of regular contractions and cervical effacement and dilatation of at least 3 cms. All women in the preterm labour group delivered before 37 weeks gestation. Blood samples were then obtained from controls, closely matched for gestational age with uncomplicated pregnancies. The preterm labour group was further stratified by cause into three groups, chorioamnionitis (n = 5), abruption (n = 4) and idiopathic (n = 11). Following organic solvent extraction, steroids were separated by HPLC and 5βDHP quantified by radioimmunoassay. Women in the idiopathic preterm labour group were found to have significantly lower circulating concentrations of 5βDHP than controls (p < 0.05). There were no significant differences found in either the chorioamnionitis or abruption groups. This result suggests that there may be a group of women in whom the normal endocrine process of labour is triggered early resulting in preterm labour.

Share and Cite:

Sheehan, P. , Rice, G. and Brennecke, S. (2014) 5β-Dihydroprogesterone and Human Preterm Labor. Open Journal of Endocrine and Metabolic Diseases, 4, 128-135. doi: 10.4236/ojemd.2014.45013.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Consultative Council of Perinatal Morbidity and Mortality, Department of Human Services Victoria, Australia, Annual Report for the Year 2006.
[2] Iams, J.D. (2003) Prediction and Early Detection of Preterm Labor. Obstetrics & Gynecology, 101, 402-412.
http://dx.doi.org/10.1016/S0029-7844(02)02505-X
[3] Meis, P.J., et al. (2003) Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesteronecaproate.[See Comment][Erratum Appears in The New England Journal of Medicine, 349, 1299]. New England Journal of Medicine, 348, 2379-2385.
http://dx.doi.org/10.1056/NEJMoa035140
[4] da Fonseca, E.B., et al. (2003) Prophylactic Administration of Progesterone by Vaginal Suppository to Reduce the Incidence of Spontaneous Preterm Birth in Women at Increased Risk: A Randomized Placebo-Controlled Double-Blind Study.[Comment]. American Journal of Obstetrics & Gynecology, 188, 419-424.
http://dx.doi.org/10.1067/mob.2003.41
[5] Grazzini, E., et al. (1998) Inhibition of Oxytocin Receptor Function by Direct Binding of Progesterone. [Comment]. Nature, 392, 509-512.
http://dx.doi.org/10.1038/33176
[6] Burger, K., Fahrenholz, F. and Gimpl, G. (1999) Non-Genomic Effects of Progesterone on the Signaling Function of G Protein-Coupled Receptors. FEBS Letters, 464, 25-29.
http://dx.doi.org/10.1016/S0014-5793(99)01668-3
[7] Astle, S., Khan, R.N. and Thornton, S. (2003) The Effects of a Progesterone Metabolite, 5 Beta-Dihydroprogesterone, on Oxytocin Receptor Binding in Human Myometrial Membranes. BJOG: An International Journal of Obstetrics &Gynaecology, 110, 589-592.
[8] Diaz-Zagoya, J.C., Wiest, W.G. and Arias, F. (1979) 20 Alpha-Hydroxysteroidoxidoreductase Activity and 20 Alpha-Dihydroprogesterone Concentration in Human Placenta before and after Parturition. American Journal of Obstetrics & Gynecology, 133, 673-676.
[9] Thornton, S., et al. (1999) Progesterone Metabolite and Spontaneous Myometrial Contractions in Vitro. Lancet, 353, 1327-1329.
http://dx.doi.org/10.1016/S0140-6736(98)05247-7
[10] Sheehan, P.M., Rice, G.E., Moses, E.K. and Brennecke, S.P. (2005) 5{beta}-Dihydroprogesterone and Steroid 5{Beta}-Reductase Decrease in Association with Human Parturition at Term. Molecular Human Reproduction, 11, 495-501.
http://dx.doi.org/10.1093/molehr/gah201
[11] Walters, D.G., Foster, P.M. and Cottrell, R.C. (1981) High-Performance Liquid Chromatography of Progesterone and Its Metabolites. Journal of Chromatography A, 219, 152-155.
http://dx.doi.org/10.1016/S0021-9673(00)80587-7
[12] Pearson Murphy, B.E., et al. (2001) Neuroactive Ring A-Reduced Metabolites of Progesterone in Human Plasma during Pregnancy: Elevated Levels of 5 Alpha-Dihydroprogesterone in Depressed Patients during the Latter Half of Pregnancy. Journal of Clinical Endocrinology & Metabolism, 86, 5981-5987.
[13] Parizek, A., et al. (2005) Neuroactivepregnanolone Isomers during Pregnancy. Journal of Clinical Endocrinology & Metabolism, 90, 395-403.
http://dx.doi.org/10.1210/jc.2004-0444
[14] Junkermann, H., Runnebaum, B. and Lisboa, B.P. (1977) New Progesterone Metabolites in Human Myometrium. Steroids, 30, 1-14.
http://dx.doi.org/10.1016/0039-128X(77)90131-3
[15] Mitchell, B.F., et al. (2005) Metabolites of Progesterone and the Pregnane X Receptor: A Novel Pathway Regulating Uterine Contractility in Pregnancy? American Journal of Obstetrics & Gynecology, 192, 1304-1313.
[16] MacDonald, P.C., Dombroski, R.A. and Casey, M.L. (1991) Recurrent Secretion of Progesterone in Large Amounts: An Endocrine/Metabolic Disorder Unique to Young Women? Endocrine Reviews, 12, 372-401.
[17] Atherden, L.M. (1959) Progesterone Metabolism; Investigation of the Products of Metabolism with Human Liver in Vitro. Biochemical Journal, 71, 411-415.
[18] Lofgren, M., Backstrom, T. and Joelsson, I. (1988) Decrease in Serum Concentration of 5 Alpha-Pregnane-3,20-dione prior to Spontaneous Labor. Acta Obstetricia et Gynecologica Scandinavica, 67, 467-470.
[19] Bloom, S.L., et al. (2001) Recurrence of Preterm Birth in Singleton and Twin Pregnancies. Obstetrics & Gynecology, 98, 379-385.
http://dx.doi.org/10.1016/S0029-7844(01)01466-1

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.