title: Revisiting the role of hCG: new regulation of the angiogenic factor EG-VEGF and its receptors.
abstract: Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor reported to be specific for endocrine tissues, including the placenta. Its biological activity is mediated via two G protein-coupled receptors, prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2). We have recently shown that (i) EG-VEGF expression peaks between the 8th and 11th weeks of gestation, (ii) its mRNA and protein levels are up-regulated by hypoxia, (iii) EG-VEGF is a negative regulator of trophoblast invasion and (iv) its circulating levels are increased in preeclampsia (PE), the most threatening pathology of pregnancy. Here, we investigated the regulation of the expression of EG-VEGF and its receptors by hCG, a key pregnancy hormone that is also deregulated in PE. During the first trimester of pregnancy, hCG and EG-VEGF exhibit the same pattern of expression, suggesting that EG-VEGF is potentially regulated by hCG. Both placental explants (PEX) and primary cultures of trophoblasts from the first trimester of pregnancy were used to investigate this hypothesis. Our results show that (i) LHCGR, the hCG receptor, is expressed both in cyto- and syncytiotrophoblasts, (ii) hCG increases EG-VEGF, PROKR1 and PROKR2 mRNA and protein expression in a dose- and time-dependent manner, (iii) hCG increases the release of EG-VEGF from PEX conditioned media, (iv) hCG effects are transcriptional and post-transcriptional and (v) the hCG effects are mediated by cAMP via cAMP response elements present in the EG-VEGF promoter region. Altogether, these results demonstrate a new role for hCG in the regulation of EG-VEGF and its receptors, an emerging regulatory system in placental development.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1036, Laboratoire Biologie du Cancer et de l'Infection, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Brouillet
authors.forename: P
authors.initials: P
authors.lastname: Hoffmann
authors.forename: S
authors.initials: S
authors.lastname: Chauvet
authors.forename: A
authors.initials: A
authors.lastname: Salomon
authors.forename: S
authors.initials: S
authors.lastname: Chamboredon
authors.forename: F
authors.initials: F
authors.lastname: Sergent
authors.forename: M
authors.initials: M
authors.lastname: Benharouga
authors.forename: J J
authors.initials: JJ
authors.lastname: Feige
authors.forename: N
authors.initials: N
authors.lastname: Alfaidy
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism* / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D008969:Molecular Sequence Data; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011974:Receptors, LH / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000235:genetics / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D017931:DNA Primers; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH; D018000:Receptors, Peptide; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived