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Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts

Fabian B Fahlbusch1*, Matthias Ruebner2, Gudrun Volkert1, Ramona Offergeld1, Andrea Hartner1, Carlos Menendez-Castro1, Reiner Strick2, Manfred Rauh1, Wolfgang Rascher1 and Jörg Dötsch3

Author Affiliations

1 Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany

2 Department of Gynecology and Obstetrics, University of Erlangen-Nürnberg, Erlangen, Germany

3 Childrens’ and Adolescents’ Hospital, University of Cologne, Cologne, Germany

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Reproductive Biology and Endocrinology 2012, 10:80  doi:10.1186/1477-7827-10-80

Published: 12 September 2012



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.


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.


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.


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.

CRH; leptin; 11beta-HSD2; Syncytin-1; Trophoblast; Syncytiotrophoblast; Placenta