Estrogen increases retrograde labeling of motoneurons: evidence of a nongenomic mechanism.
Estrogen has a variety of neurotrophic effects mediated via different signaling cascades, including ERK and phosphatidylinositol 3-kinase (PI3K) pathways. In this study, we investigated effects of estrogen and inhibitors for ERK and PI3K applied directly onto the cut sciatic nerve on retrograde labeling of lumbar motoneurons. A mix of retrograde tracer (Fluorogold) and 17beta-estradiol, in combination with an antagonist for estrogen receptors ICI 182,780, an inhibitor of ERK1/2 pathway (U0126), an inhibitor of PI3K (LY-294002), or a protein synthesis inhibitor (cycloheximide), was applied to the proximal stump of the transected sciatic nerve for 24 h. Coapplication of Fluorogold with 17beta-estradiol produced a significant increase in the number of retrograde-labeled lumbar motoneurons, compared with Fluorogold alone. Estrogen potentiation of retrograde labeling was inhibited by application of ICI 182,780, U0126, LY-294002, and cycloheximide. Immunohistochemical analysis of the sciatic nerve, 24 h following crush injury, revealed accumulation of phospho-ERK in regenerating nerve fibers. The data suggest a role for estrogen, ERK, PI3K, and protein synthesis in the uptake and retrograde transport of Fluorogold. We propose that estrogen action in peripheral nerve fibers is mediated via the ERK and PI3K signaling pathways and is reliant on local protein synthesis.
Murashov
Alexander K
AK
Department of Physiology, Brody School of Medicine, East Carolina University, Brody Bldg. #6N-98, 600 Moye Blvd., Greenville, NC 27858, USA. murashoval@mail.ecu.edu
Islamov
Rustem R
RR
McMurray
Roger J
RJ
Pak
Elena S
ES
Weidner
Douglas A
DA
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects* / Q000201:enzymology; D009409:Nerve Crush; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013266:Stilbamidines / Q000493:pharmacokinetics; D014316:Tritium
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D009025:Morpholines; D009570:Nitriles; D011960:Receptors, Estrogen; D013266:Stilbamidines; C113580:U 0126; D014316:Tritium; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases