title: Elevated glucocorticoid metabolism in placental tissue from first trimester pregnancies at increased risk of pre-eclampsia.
abstract: BACKGROUND
  The local actions of glucocorticoids in the placenta can be modulated by 11β-hydroxysteroid dehydrogenase (11βHSD) enzymes, which catalyse inter-conversion of cortisol with its inert metabolite, cortisone, and are known to be expressed in the term placenta and decidua. However, the expression and activity of these enzymes have not been well characterised in the first trimester placenta. The aim of this study was to compare 11βHSD2 expression and activity in first trimester placental tissue from pregnancies at either relatively low or high risk of developing pre-eclampsia as determined by Doppler ultrasound.
  
  
  METHODS
  Enzyme expression was assessed by western blot analysis and immunohistochemistry while 11βHSD enzyme activities were quantified using radiometric conversion of [3H]-cortisol in the presence of NADP(+) or NAD(+).
  
  
  RESULTS
  11βHSD2 was expressed in syncytiotrophoblast of first trimester placenta, and there was no difference in the level of expression of placental 11βHSD2 protein between 9 high pre-eclampsia risk and 14 low pre-eclampsia risk pregnancies. NAD(+)-dependent cortisol oxidation was elevated 3-fold in placental tissue from pregnancies at higher risk of pre-eclampsia than in normal pregnancies (50.9 ± 15.9 versus 18.3 ± 1.9 pmol cortisone/mg protein.10 min, n = 11 & 12, respectively; P < 0.05).
  
  
  CONCLUSIONS
  Expression of 11βHSD2 is thought to protect the fetus from exposure to maternal cortisol. While other studies have suggested that 11βHSD2 is down regulated in term pre-eclamptic placentae, our study suggests that there is increased cortisol inactivation in first trimester placenta prior to week 10 of gestation, from pregnancies at higher risk of developing pre-eclampsia.
authors.affiliation: Fetal Medicine Unit, St.George's Hospital, Blackshaw Road, London SW17 0QT, UK; Division of Clinical Sciences, St.George's, University of London, Cranmer Terrace, London SW17 0RE, UK. Electronic address: smukherj@sgul.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Biomedical Sciences, St.George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: James
authors.affiliation: Fetal Medicine Unit, St.George's Hospital, Blackshaw Road, London SW17 0QT, UK; Division of Clinical Sciences, St.George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: B
authors.initials: B
authors.lastname: Thilaganathan
authors.affiliation: Division of Biomedical Sciences, St.George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: G St J
authors.initials: GSJ
authors.lastname: Whitley
authors.affiliation: Division of Biomedical Sciences, St.George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Michael
authors.affiliation: Division of Biomedical Sciences, St.George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Cartwright
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D003348:Cortisone / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012306:Risk; D016216:Ultrasonography, Prenatal
chemical_list: D005938:Glucocorticoids; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003348:Cortisone; D006854:Hydrocortisone