title: Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH.
abstract: Although ACTH is important to adrenal growth and steroidogenesis, its role in vascular development and function has not been established in vivo. In the present study, we demonstrate the expression of mRNA for all four VEGF isoforms (mVEGF(120,144,164,188)) and for Flk-1/KDR and Flt-1 receptors in the mouse adrenal in vivo. Suppression of the pituitary adrenocortical axis by dexamethasone (0.5 mg x 100 g body wt(-1) x day(-1) during 6 days) induced a decrease in corticosterone levels, adrenal weights by 50% (P < 0.001), VEGF(188) mRNA, and Flk-1/KDR mRNA, whereas Flt-1 remained consistent during steroid treatment. A daily injection of ACTH-(1-39) restored the transcript for Flk-1/KDR and both VEGF(188) and plasma corticosterone to control levels. To gain further insights into the effects of ACTH, cultured endothelial cells (ECs) were treated with forskolin, which increases cAMP, the second messenger in ACTH action. We demonstrate that Flk-1/KDR protein expression was markedly increased by forskolin within 24-48 h of treatment in a dose-dependent manner (0.1-10 microM). The biological effect of ACTH on ECs was then tested by use of coincubations of fasciculata cells and ECs in 3D-collagen assay. Within 5-7 days of culture, ECs organized into multicellular structures that resemble networks of microvasculature, which characterize angiogenesis in vitro.
authors.affiliation: Equipe Mixte Institut National de la Santé et de la Recherche Médicale (EMI) 01-05 Angio, 38054 Grenoble, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Mallet
authors.forename: Olivier
authors.initials: O
authors.lastname: Feraud
authors.forename: Gaehl
authors.initials: G
authors.lastname: Ouengue-Mbele
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gaillard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sappay
authors.forename: Daniel
authors.initials: D
authors.lastname: Vittet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vilgrain
mesh_terms: D000302:Adrenal Cortex / Q000098:blood supply; D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001284:Atrophy; D001483:Base Sequence; D015153:Blotting, Western; D002196:Capillaries / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000235:genetics; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008222:Lymphokines / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005576:Colforsin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2