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Rapid actions of estradiol on cyclic amp response-element binding protein phosphorylation in dorsal root ganglion neurons.
Neuroscience. 2004; 129(3):629-37.N

Abstract

Actions of gonadal steroids have not been widely investigated in the peripheral nervous system, although many dorsal root ganglion (DRG) and autonomic pelvic ganglion (PG) neurons express estrogen receptors (ERs). We have studied the effects of 17beta-estradiol exposure on cultured DRG and PG neurons from adult rats. Western blotting analysis of DRG extracts detected phosphorylation of ERK1 and ERK2 (extracellular signal-regulated kinases) that peaked 10 min after exposure to 17beta-estradiol. These extracts contain both neurons and glia; therefore, to determine if this response occurred in DRG neurons, we developed an immunocytochemical method to specifically measure activation in individual neurons. These measurements showed that estradiol increased phosphorylation of CREB (cyclic AMP response-element binding protein), which was consistently blocked by the ERK pathway inhibitor PD98059 but not by the inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002. 17beta-Estradiol activation of CREB in DRG neurons was reduced by the ER antagonist, ICI182780. In contrast, in PG neurons estradiol did not affect CREB phosphorylation, highlighting a difference in E2 responses in different populations of peripheral neurons. This study has shown that estrogens can rapidly activate signaling pathways associated with CREB-mediated transcriptional regulation in sensory neurons. As these pathways also mediate many effects of neurotrophic factors, changes in estrogen levels (e.g. during puberty, pregnancy or menopause) could have broad-ranging genomic and non-genomic actions on urogenital pain sensation and reflex pathways.

Authors+Show Affiliations

Prince of Wales Medical Research Institute, University of New South Wales, Sydney, Australia.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15541884

Citation

Purves-Tyson, T D., and J R. Keast. "Rapid Actions of Estradiol On Cyclic Amp Response-element Binding Protein Phosphorylation in Dorsal Root Ganglion Neurons." Neuroscience, vol. 129, no. 3, 2004, pp. 629-37.
Purves-Tyson TD, Keast JR. Rapid actions of estradiol on cyclic amp response-element binding protein phosphorylation in dorsal root ganglion neurons. Neuroscience. 2004;129(3):629-37.
Purves-Tyson, T. D., & Keast, J. R. (2004). Rapid actions of estradiol on cyclic amp response-element binding protein phosphorylation in dorsal root ganglion neurons. Neuroscience, 129(3), 629-37.
Purves-Tyson TD, Keast JR. Rapid Actions of Estradiol On Cyclic Amp Response-element Binding Protein Phosphorylation in Dorsal Root Ganglion Neurons. Neuroscience. 2004;129(3):629-37. PubMed PMID: 15541884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid actions of estradiol on cyclic amp response-element binding protein phosphorylation in dorsal root ganglion neurons. AU - Purves-Tyson,T D, AU - Keast,J R, PY - 2004/08/11/accepted PY - 2004/11/16/pubmed PY - 2005/3/8/medline PY - 2004/11/16/entrez SP - 629 EP - 37 JF - Neuroscience JO - Neuroscience VL - 129 IS - 3 N2 - Actions of gonadal steroids have not been widely investigated in the peripheral nervous system, although many dorsal root ganglion (DRG) and autonomic pelvic ganglion (PG) neurons express estrogen receptors (ERs). We have studied the effects of 17beta-estradiol exposure on cultured DRG and PG neurons from adult rats. Western blotting analysis of DRG extracts detected phosphorylation of ERK1 and ERK2 (extracellular signal-regulated kinases) that peaked 10 min after exposure to 17beta-estradiol. These extracts contain both neurons and glia; therefore, to determine if this response occurred in DRG neurons, we developed an immunocytochemical method to specifically measure activation in individual neurons. These measurements showed that estradiol increased phosphorylation of CREB (cyclic AMP response-element binding protein), which was consistently blocked by the ERK pathway inhibitor PD98059 but not by the inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002. 17beta-Estradiol activation of CREB in DRG neurons was reduced by the ER antagonist, ICI182780. In contrast, in PG neurons estradiol did not affect CREB phosphorylation, highlighting a difference in E2 responses in different populations of peripheral neurons. This study has shown that estrogens can rapidly activate signaling pathways associated with CREB-mediated transcriptional regulation in sensory neurons. As these pathways also mediate many effects of neurotrophic factors, changes in estrogen levels (e.g. during puberty, pregnancy or menopause) could have broad-ranging genomic and non-genomic actions on urogenital pain sensation and reflex pathways. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/15541884/Rapid_actions_of_estradiol_on_cyclic_amp_response_element_binding_protein_phosphorylation_in_dorsal_root_ganglion_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(04)00732-8 DB - PRIME DP - Unbound Medicine ER -