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Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium
Author(s) -
Berndt Sarah,
Perrier d'Hauterive Sophie,
Blacher Silvia,
Péqueux Christel,
Lorquet Sophie,
Munaut Carine,
Applanat Martine,
Astrid Hervé Marie,
Lamandé Noël,
Corvol Pierre,
Brûle Frédéric,
Frankenne Françis,
Poutanen Matti,
Huhtaniemi Ilpo,
Geenen Vincent,
Noël Agnès,
Foidart JeanMichel
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-5885fje
Subject(s) - angiogenesis , trophoblast , medicine , endocrinology , human chorionic gonadotropin , paracrine signalling , matrigel , autocrine signalling , biology , vascular endothelial growth factor , chemistry , receptor , placenta , hormone , fetus , pregnancy , vegf receptors , genetics
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 chorioallantöıc 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 anti‐body (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.—Berndt, S., Perrier d'Hauterive, S., Blacher, S., Péqueux, C., Lorquet, S., Munaut, C., Applanat, M., Hervé, M. A., Lamandé, N., Corvol, P., van den Brûle, F., Frankenne, F., Poutanen, M., Huhtaniemi, I., Geenen, V., Noël, A., Foidart, J.‐M. Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium. FASEB J. 20, E2189–E2198 (2006)