title: Expression of eight glucocorticoid receptor isoforms in the human preterm placenta vary with fetal sex and birthweight.
abstract: BACKGROUND
  Administration of betamethasone to women at risk of preterm delivery is known to be associated with reduced fetal growth via alterations in placental function and possibly direct effects on the fetus. The placental glucocorticoid receptor (GR) is central to this response and recent evidence suggests there are numerous isoforms for GR in term placentae. In this study we have questioned whether GR isoform expression varies in preterm placentae in relation to betamethasone exposure, fetal sex and birthweight.
  
  
  METHODS
  Preterm (24-36 completed weeks of gestation, n = 55) and term placentae (>37 completed weeks of gestation, n = 56) were collected at delivery. Placental GR expression was examined using Western Blot and analysed in relation to gestational age at delivery, fetal sex, birthweight and betamethasone exposure. Data was analysed using non-parametric tests.
  
  
  RESULTS
  Eight known isoforms of the GR were detected in the preterm placenta and include GRα (94 kDa), GRβ (91 kDa), GRα C (81 kDa) GR P (74 kDa) GR A (65 kDa), GRα D1-3 (50-55 kDa). Expression varied between preterm and term placentae with a greater expression of GRα C in preterm placentae relative to term placentae. The only sex differences in preterm placentae was that GRα D2 expression was higher in males than females. There were no alterations in preterm placental GR expression in association with betamethasone exposure.
  
  
  CONCLUSIONS
  GRα C is the isoform involved in glucocorticoid induced apoptosis and suggests that its predominance in preterm placentae may contribute to the pathophysiology of preterm birth.
authors.affiliation: Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Z
authors.initials: Z
authors.lastname: Saif
authors.affiliation: Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors.forename: N A
authors.initials: NA
authors.lastname: Hodyl
authors.affiliation: Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Stark
authors.affiliation: Endocrinology, Monash Health, MIMR-PHI Institute, Monash University, Melbourne, VIC, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Fuller
authors.affiliation: Department of Biochemistry & Molecular Biology, Faculty of Medicine, Monash University, Clayton, VIC, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Cole
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Lu
authors.affiliation: Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia. Electronic address: Vicki.clifton@adelaide.edu.au.
authors.forename: V L
authors.initials: VL
authors.lastname: Clifton
mesh_terms: D001623:Betamethasone / Q000494:pharmacology; D001724:Birth Weight; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008297:Male; D010920:Placenta / Q000737:chemistry* / Q000187:drug effects; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism*; D020033:Protein Isoforms / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000032:analysis*; D012727:Sex Characteristics; D047929:Term Birth / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D001623:Betamethasone
keywords: Fetal growth; Glucocorticoid receptor; Placenta; Pregnancy; Preterm; Sex