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.
Copyright 2007 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Homeostasis / drug effects
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Homeostasis / physiology
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Membrane Proteins / drug effects
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Membrane Proteins / metabolism
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Mitogen-Activated Protein Kinase 3 / drug effects
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Mitogen-Activated Protein Kinase 3 / metabolism
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Neuroglia / cytology
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Neuroglia / drug effects
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Neuroglia / metabolism*
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Phosphatidylinositol 3-Kinases / drug effects
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Phosphatidylinositol 3-Kinases / metabolism
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Progesterone / pharmacology
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Progesterone / physiology*
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Protein Kinase C / drug effects
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Protein Kinase C / metabolism
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Receptors, Progesterone / drug effects
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Receptors, Progesterone / metabolism
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Retina / cytology
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Retina / drug effects
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Retina / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Sus scrofa
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Vascular Endothelial Growth Factor A / genetics*
Substances
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Membrane Proteins
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PGRMC1 protein, human
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RNA, Messenger
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Receptors, Progesterone
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Vascular Endothelial Growth Factor A
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Progesterone
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Phosphatidylinositol 3-Kinases
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Protein Kinase C
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Mitogen-Activated Protein Kinase 3