Metabolism of Synthetic Steroids by the Human Placenta

Murphy, V.E.; Fittock, R.J.; Zarzycki, P.K.; Delahunty, M.M.; Smith, R.; Clifton, V.L.

doi:10.1016/j.placenta.2005.12.010

« Previous Next »Placenta
Volume 28, Issue 1 , Pages 39-46, January 2007

Metabolism of Synthetic Steroids by the Human Placenta

V.E. Murphy
- Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia
- Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia
R.J. Fittock
- Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia
P.K. Zarzycki
- Laboratory of Toxicology, Department of Environmental Biology, Technical University of Koszalin, Koszalin, Poland
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Medical University of Gdańsk, Gdańsk, Poland
M.M. Delahunty
- Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia
R. Smith
- Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia
V.L. Clifton
- Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia
- Corresponding author. Mothers and Babies Research Centre, Endocrine Unit, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, New South Wales 2310, Australia. Tel.: +61 2 4921 4380; fax: +61 2 4921 4394.

Accepted 22 December 2005.

Abstract

Pregnant women with asthma are frequently exposed to synthetic glucocorticoids and glucocorticoids are known to reduce fetal growth. The fetus is normally protected from the harmful effects of maternally derived glucocorticoids by the placental enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Whether 11β-HSD2 inactivates the synthetic glucocorticoids used for asthma treatment during pregnancy (budesonide, beclomethasone dipropionate and fluticasone propionate) remains unknown.

To investigate the relationship between steroid use during pregnancy and fetal growth and development, pregnant women with (n=119) and without asthma (n=84) were followed throughout pregnancy. Data on asthma medication use, neonatal size at birth, placental weight and cord blood cortisol and estriol were collected. Placental tissue samples were collected from non-asthmatic women (n=8) for metabolism studies. Placental 11β-HSD2 activity was determined using beclomethasone dipropionate, budesonide, fluticasone propionate, prednisolone, dexamethasone and betamethasone as steroid substrates. Steroids and their oxidised metabolites were examined using thin layer chromatography and densitometry.

Placental 11β-HSD2 metabolised beclomethasone, prednisolone, dexamethasone and betamethasone, but not budesonide or fluticasone. No association between the use of inhaled steroids for asthma treatment during pregnancy and alterations in neonatal size, placental weight, gestational age at delivery, or umbilical vein estriol concentrations was demonstrated compared to non-asthmatic women. In conclusion, the use of inhaled steroids for asthma treatment does not affect fetal growth, despite differences in placental metabolism by 11β-HSD2.

Keywords: Glucocorticoid, Pregnancy, Asthma, Budesonide, Beclomethasone, Fluticasone, 11β-Hydroxysteroid dehydrogenase