title: Dexamethasone stimulates the expression of leptin and 11β-HSD2 in primary human placental trophoblastic cells.
abstract: OBJECTIVE
  Fetal glucocorticoid excess is thought to play an important role in early-life programming, promoting growth restriction and contributing to adult metabolic, cardiovascular and neuroendocrine disease. We hypothesized that dexamethasone incubation of primary trophoblastic cells from human healthy placentas at term might induce altered gene and protein expression of several endocrine placental regulators.
  
  
  METHODS
  Primary villous trophoblastic cells were incubated with 10 μM dexamethasone for 6, 12, 24, 48 and 72 h. Non-incubated trophoblastic cells served as vehicle control. Gene expression of leptin, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and insulin-like growth factor-binding protein-1 (IGFBP-1) was measured. Moreover, leptin, β-human chorionic gonadotropine (β-hCG) and lactate dehydrogenase (LDH) release into the culture medium was determined.
  
  
  RESULTS
  Leptin gene expression was significantly increased in dexamethasone-incubated trophoblastic cells after 24, 48 and 72 h. There was a significant increase in leptin concentration in the medium of the cell culture after 48 h. Gene expression of 11β-HSD2 was significantly higher in dexamethasone-stimulated trophoblastic cells compared to vehicle controls after 72 h. The expression rate of IGFBP-1 mRNA was basal throughout the incubation period. The concentration of β-HCG in the supernatant increased significantly after 72 h of dexamethasone incubation, while LDH concentrations remained stable.
  
  
  CONCLUSIONS
  Our findings suggest that dexamethasone incubation stimulates leptin and 11β-HSD2 gene expression in primary villous trophoblastic cells of healthy human placentas, while enhancing cytotrophoblast differentiation.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, University of Erlangen-Nuremberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Tzschoppe
authors.forename: Fabian
authors.initials: F
authors.lastname: Fahlbusch
authors.forename: Julia
authors.initials: J
authors.lastname: Seidel
authors.forename: Helmuth G
authors.initials: HG
authors.lastname: Dörr
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Tamme W
authors.initials: TW
authors.lastname: Goecke
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Ralf L
authors.initials: RL
authors.lastname: Schild
authors.forename: Ellen
authors.initials: E
authors.lastname: Struwe
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D005938:Glucocorticoids; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D020738:Leptin; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D003907:Dexamethasone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human