title: Membrane-initiated effects of progesterone on calcium dependent signaling and activation of VEGF gene expression in retinal glial cells.
abstract: Neurosteroids, such as progesterone, influence central nervous system development and function by regulating a broad spectrum of physiological processes. Here, we investigated membrane-initiated actions of progesterone in the retina and identified the membrane-associated progesterone receptor component 1 (PGRMC1). We found PGRMC1 expressed mainly in retinal Muller glia (RMG) and retinal pigment epithelium, and localized uniquely to microsomal and plasma membrane fractions. In RMG, membrane-impermeable progesterone conjugate induced calcium influx and subsequent phosphatidylinositol 3-kinase-mediated phosphorylation of PKC and ERK-1/2. Induction by progesterone also led to PKC-dependent activation of VEGF gene expression and protein synthesis, suggesting a contribution of membrane-initiated hormone effects to VEGF induced neovascularization within retina.
authors.affiliation: Institute of Human Genetics, GSF National-Research Center for Environment and Health, Neuherberg, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Swiatek-De Lange
authors.forename: Andreas
authors.initials: A
authors.lastname: Stampfl
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.forename: Hans
authors.initials: H
authors.lastname: Zischka
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Gloeckner
authors.forename: Cornelia A
authors.initials: CA
authors.lastname: Deeg
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D034421:Sus scrofa; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D042461:Vascular Endothelial Growth Factor A; D011374:Progesterone; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D048052:Mitogen-Activated Protein Kinase 3