title: Effect of heparin-binding EGF-like growth factor and amphiregulin on the MAP kinase-induced production of vascular endothelial growth factor by human granulosa cells.
abstract: The function of granulosa cells is regulated by various hormones and growth factors. Our aim is to clarify the regulation of vascular endothelial growth factor (VEGF) production induced by heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR) in a human granulosa cell line, KGN. KGN cells were cultured and incubated for 24 h with HB-EGF and AR. The levels of VEGF in the culture media were measured by an enzyme-linked immunosorbent assay. The activation of MAP kinase in KGN cells was detected by Western blot analysis. VEGF production was significantly increased by HB-EGF or AR alone in a dose-dependent manner, whereas it was decreased by AG1478 or U0126. The MAP kinase activity was increased by treatment with HB-EGF or AR. The results suggested that VEGF is induced by HB-EGF and AR through mechanisms involving MAP kinase. The increase in VEGF may contribute to neovascularization, which in turn would promote various ovulation phenomena as well as follicular growth.
authors.affiliation: Department of Obstetrics and Gynecology, Oita University, Japan.
authors.forename: Sinya
authors.initials: S
authors.lastname: Karakida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawano
authors.forename: Yufuko
authors.initials: Y
authors.lastname: Utsunomiya
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narahara
mesh_terms: D066258:Amphiregulin; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D066255:EGF Family of Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D006107:Granulosa Cells / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis*
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D002070:Butadienes; D066255:EGF Family of Proteins; D006023:Glycoproteins; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D009570:Nitriles; D011799:Quinazolines; D020032:Tyrphostins; C113580:U 0126; D042442:Vascular Endothelial Growth Factors; C101044:RTKI cpd; D020928:Mitogen-Activated Protein Kinases