title: Endothelial cells regulate β-catenin activity in adrenocortical cells via secretion of basic fibroblast growth factor.
abstract: Endothelial cell-derived products influence the synthesis of aldosterone and cortisol in human adrenocortical cells by modulating proteins such as steroidogenic acute-regulatory (StAR) protein, steroidogenic factor (SF)-1 and CITED2. However, the potential endothelial cell-derived factors that mediate this effect are still unknown. The current study was perfomed to look into the control of β-catenin activity by endothelial cell-derived factors and to identify a mechanism by which they affect β-catenin activity in adrenocortical NCIH295R cells. Using reporter gene assays and Western blotting, we found that endothelial cell-conditioned medium (ECCM) led to nuclear translocation of β-catenin and an increase in β-catenin-dependent transcription that could be blocked by U0126, an inhibitor of the mitogen-activated protein kinase pathway. Furthermore, we found that a receptor tyrosin kinase (RTK) was involved in ECCM-induced β-catenin-dependent transcription. Through selective inhibition of RTK using Su5402, it was shown that receptors responding to basic fibroblast growth factor (bFGF) mediate the action of ECCM. Adrenocortical cells treated with bFGF showed a significant greater level of bFGF mRNA. In addition, HUVECs secrete bFGF in a density-dependent manner. In conclusion, the data suggest that endothelial cells regulate β-catenin activity in adrenocortical cells also via secretion of basic fibroblast growth factor.
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, Heinrich-Heine University Dusseldorf, D-40225 Dusseldorf, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Schwafertz
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, Heinrich-Heine University Dusseldorf, D-40225 Dusseldorf, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Schinner
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, Heinrich-Heine University Dusseldorf, D-40225 Dusseldorf, Germany.
authors.forename: Markus C
authors.initials: MC
authors.lastname: Kühn
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, Heinrich-Heine University Dusseldorf, D-40225 Dusseldorf, Germany; Department of Medicine III, Carl Gustav Carus Medical School, University of Technology, D-01307 Dresden, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Haase
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, Heinrich-Heine University Dusseldorf, D-40225 Dusseldorf, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Asmus
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, Heinrich-Heine University Dusseldorf, D-40225 Dusseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Mülders-Opgenoorth
authors.affiliation: Department of Medicine III, Carl Gustav Carus Medical School, University of Technology, D-01307 Dresden, Germany; Department of Molecular Medicine and Surgery, L1:01 Rolf Luft Centrum, Karolinska Institute, Stockholm, Sweden.
authors.forename: Ishrath
authors.initials: I
authors.lastname: Ansurudeen
authors.affiliation: Department of Physiology and Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hornsby
authors.affiliation: Department of Medicine III, Carl Gustav Carus Medical School, University of Technology, D-01307 Dresden, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Morawietz
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Pharmacology for Pharmacist's Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Oetjen
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, Heinrich-Heine University Dusseldorf, D-40225 Dusseldorf, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schott
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, Heinrich-Heine University Dusseldorf, D-40225 Dusseldorf, Germany; Division of Endocrinology and Metabolism, Rostock University Medical Center, Germany. Electronic address: Holger.Willenberg@uni-rostock.de.
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology*; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D051176:beta Catenin; D016222:Fibroblast Growth Factor 2; D008156:Luciferases; D011494:Protein Kinases
keywords: Adrenal gland; Aldosterone; Basic fibroblast growth factor; Beta-catenin; CITED2