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

Reproductive Biology and Endocrinology

Research

Jörg Dötsch¹  Matthias Ruebner²  Reiner Strick²  Carlos Menendez-Castro³  Gudrun Volkert³  Fabian B Fahlbusch³  Andrea Hartner³  Ramona Offergeld³  Manfred Rauh³  Wolfgang Rascher³ 

[1] Childrens’ and Adolescents’ Hospital, University of Cologne, Cologne,, Germany;Department of Gynecology and Obstetrics, University of Erlangen-Nürnberg, Erlangen,, Germany;Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen,, Germany;

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

DOI  :  10.1186/1477-7827-10-80

 received in 2012-01-13, accepted in 2012-09-04,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsWe 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.ResultsCRH 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.ConclusionThe 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.

【 授权许可】

CC BY   
© Fahlbusch et al.; licensee BioMed Central Ltd. 2012