title: Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts.
abstract: BACKGROUND
  The placental syncytiotrophoblast is the major source of maternal plasma corticotropin-releasing hormone (CRH) in the second half of pregnancy. Placental CRH exerts multiple functions in the maternal organism: It induces the adrenal secretion of cortisol via the stimulation of adrenocorticotropic hormone, regulates the timing of birth via its actions in the myometrium and inhibits the invasion of extravillous trophoblast cells in vitro. However, the auto- and paracrine actions of CRH on the syncytiotrophoblast itself are unknown. Intrauterine growth restriction (IUGR) is accompanied by an increase in placental CRH, which could be of pathophysiological relevance for the dysregulation in syncytialisation seen in IUGR placentas.
  
  
  METHODS
  We aimed to determine the effect of CRH on isolated primary trophoblastic cells in vitro. After CRH stimulation the trophoblast syncytialisation rate was monitored via syncytin-1 gene expression and beta-hCG (beta-human chorionic gonadotropine) ELISA in culture supernatant. The expression of the IUGR marker genes leptin and 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) was measured continuously over a period of 72 h. We hypothesized that CRH might attenuate syncytialisation, induce leptin, and reduce 11beta-HSD2 expression in primary villous trophoblasts, which are known features of IUGR.
  
  
  RESULTS
  CRH did not influence the differentiation of isolated trophoblasts into functional syncytium as determined by beta-hCG secretion, albeit inducing syncytin-1 expression. Following syncytialisation, CRH treatment significantly increased leptin and 11beta-HSD2 expression, as well as leptin secretion into culture supernatant after 48 h.
  
  
  CONCLUSIONS
  The relevance of CRH for placental physiology is underlined by the present in vitro study. The induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by CRH might promote fetal nutrient supply and placental corticosteroid metabolism in the phase before labour induction.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany. fabian.fahlbusch@uk-erlangen.de
authors.forename: Fabian B
authors.initials: FB
authors.lastname: Fahlbusch
authors.forename: Matthias
authors.initials: M
authors.lastname: Ruebner
authors.forename: Gudrun
authors.initials: G
authors.lastname: Volkert
authors.forename: Ramona
authors.initials: R
authors.lastname: Offergeld
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
authors.forename: Carlos
authors.initials: C
authors.lastname: Menendez-Castro
authors.forename: Reiner
authors.initials: R
authors.lastname: Strick
authors.forename: Manfred
authors.initials: M
authors.lastname: Rauh
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015686:Gene Products, env / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: C101531:CRF receptor type 2; D015686:Gene Products, env; D020738:Leptin; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C405335:syncytin; D003346:Corticotropin-Releasing Hormone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2