1. Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium
- Author
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Sarah Berndt, Sophie Perrier d'Hauterive, Silvia Blacher, Christel Péqueux, Sophie Lorquet, Carine Munaut, Martine Applanat, Marie Astrid Hervé, Noël Lamandé, Pierre Corvol, Frédéric Brûle, Françis Frankenne, Matti Poutanen, Ilpo Huhtaniemi, Vincent Geenen, Agnès Noël, Jean‐Michel Foidart, and Astrid Marie Hervé
- Subjects
endocrine system ,Time Factors ,Angiogenesis ,Neovascularization, Physiologic ,Chick Embryo ,Endometrium ,Chorionic Gonadotropin ,Biochemistry ,Chorioallantoic Membrane ,Human chorionic gonadotropin ,Tissue Culture Techniques ,Mice ,Human placental lactogen ,Genetics ,medicine ,Animals ,Humans ,Protein kinase A ,Molecular Biology ,Aorta ,reproductive and urinary physiology ,Cell Proliferation ,Mice, Knockout ,Dose-Response Relationship, Drug ,urogenital system ,Chemistry ,luteinizing hormone/choriogonadotropin receptor ,Endothelial Cells ,Trophoblast ,Epithelial Cells ,Receptors, LH ,Molecular biology ,Rats ,Mice, Inbred C57BL ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,Female ,hormones, hormone substitutes, and hormone antagonists ,Biotechnology - Abstract
Successful embryo development requires an extensive endometrial angiogenesis in proximity of implantation site. The glycoprotein hCG is produced even before implantation by trophoblast in normal pregnancy. In this manuscript, we demonstrate an angiogenic effect of hCG in several in vivo (chick chorioallantoïc membrane, matrigel plug assay, aortic ring assay) and in vitro experimental models. In contrast, human placental lactogen (hPL) did not display angiogenic properties. LH/hCG receptor was detected in endothelial cells by reverse-transcriptase polymerase chain reaction (RT-PCR) and by Western blotting. In mice aortic ring assay, angiostimulation by hCG was abrogated by deletion of LH/hCG receptor (LuRKO mice). Use of recombinant hCG and anti-hCG antibody (Ab) further confirmed the specificity of this angiogenic activity. By using dibutyryl cAMP, adenylate cyclase, or protein kinase A inhibitors, we demonstrate that hCG-mediated angiogenesis involves adenylyl-cyclase-protein kinase A activation. Addition of hCG to endometrial epithelial epithelial cells, but not to cultured endothelial cells, stimulated vascular endothelial growth factor (VEGF). VEGF and hCG also displayed additive activities. Altogether, these data demonstrate that peritrophoblastic angiostimulation may result from a paracrine dialogue between trophoblast, epithelial, and endothelial cells through hCG and VEGF.
- Published
- 2006
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