Membrane-initiated effects of progesterone on calcium dependent signaling and activation of VEGF gene expression in retinal glial cells.
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.
Swiatek-De Lange
Magdalena
M
Institute of Human Genetics, GSF National-Research Center for Environment and Health, Neuherberg, Germany.
Stampfl
Andreas
A
Hauck
Stefanie M
SM
Zischka
Hans
H
Gloeckner
Christian J
CJ
Deeg
Cornelia A
CA
Ueffing
Marius
M
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*
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