title: Pigment epithelium-derived factor regulation by human chorionic gonadotropin in granulosa cells.
abstract: Human chorionic gonadotropin (hCG) is a known trigger of ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication of assisted reproduction. Administration of hCG results in the release of vascular endothelial growth factor (VEGF) from the ovary. We have previously shown that expression of pigment epithelium-derived factor (PEDF) in granulosa cell line is regulated by hCG, reciprocally to VEGF, and that the PEDF-VEGF balance is impaired in OHSS. Our aim was to explore the signaling network by which hCG downregulates the expression of PEDF mRNA and protein in granulosa cells. We applied specific chemical inhibitors and stimuli to human primary granulosa cells and rat granulosa cell line. We found that PKA and protein kinase C, as well as EGFR, ERK1/2 and PI3K, participate in the signaling network. The finding that hCG-induced PEDF downregulation and VEGF upregulation are mediated by similar signaling cascades emphasizes the delicate regulation of ovarian angiogenesis.
authors.affiliation: Department of Cell and Developmental BiologySackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelIVF and Infertility UnitDepartment of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraelSackler Faculty of MedicineTel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Bar-Joseph
authors.affiliation: Department of Cell and Developmental BiologySackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelIVF and Infertility UnitDepartment of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraelSackler Faculty of MedicineTel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel Department of Cell and Developmental BiologySackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelIVF and Infertility UnitDepartment of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraelSackler Faculty of MedicineTel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Ben-Ami
authors.affiliation: Department of Cell and Developmental BiologySackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelIVF and Infertility UnitDepartment of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraelSackler Faculty of MedicineTel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel Department of Cell and Developmental BiologySackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelIVF and Infertility UnitDepartment of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraelSackler Faculty of MedicineTel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel.
authors.forename: Raphael
authors.initials: R
authors.lastname: Ron-El
authors.affiliation: Department of Cell and Developmental BiologySackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelIVF and Infertility UnitDepartment of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraelSackler Faculty of MedicineTel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Shalgi
authors.affiliation: Department of Cell and Developmental BiologySackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelIVF and Infertility UnitDepartment of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraelSackler Faculty of MedicineTel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel chuderla@gmail.com.
authors.forename: Dana
authors.initials: D
authors.lastname: Chuderland
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018773:Genes, erbB-1 / Q000502:physiology; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000098:blood supply / Q000187:drug effects; D051381:Rats; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D006063:Chorionic Gonadotropin; D017868:Cyclic AMP-Dependent Protein Kinases; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor