Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice.
Identifieur interne : 001229 ( Main/Exploration ); précédent : 001228; suivant : 001230Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice.
Auteurs : Pu Hu [États-Unis] ; Ji Liu [États-Unis] ; Ali Yasrebi [États-Unis] ; Juliet D. Gotthardt [États-Unis] ; Nicholas T. Bello [États-Unis] ; Zhiping P. Pang [États-Unis] ; Troy A. Roepke [États-Unis]Source :
- Endocrinology [ 1945-7170 ] ; 2016.
Descripteurs français
- KwdFr :
- Acrylamides, Anilides (métabolisme), Animaux, Corticolibérine, Cyclic AMP-Dependent Protein Kinases (métabolisme), Femelle, Neurones (physiologie), Nitriles, Noyau paraventriculaire de l'hypothalamus (physiologie), Oestradiol (physiologie), Potentiels post-synaptiques excitateurs, Propionates, Protein kinase C-delta (métabolisme), Souris de lignée C57BL, Souris knockout, Sous-unités alpha Gq-G11 des protéines G (métabolisme), Transduction du signal, Type C Phospholipases (métabolisme).
- MESH :
- métabolisme : Anilides, Cyclic AMP-Dependent Protein Kinases, Protein kinase C-delta, Sous-unités alpha Gq-G11 des protéines G, Type C Phospholipases.
- physiologie : Neurones, Noyau paraventriculaire de l'hypothalamus, Oestradiol.
- Acrylamides, Animaux, Corticolibérine, Femelle, Nitriles, Potentiels post-synaptiques excitateurs, Propionates, Souris de lignée C57BL, Souris knockout, Transduction du signal.
English descriptors
- KwdEn :
- Acrylamides, Anilides (metabolism), Animals, Corticotropin-Releasing Hormone, Cyclic AMP-Dependent Protein Kinases (metabolism), Estradiol (physiology), Excitatory Postsynaptic Potentials, Female, GTP-Binding Protein alpha Subunits, Gq-G11 (metabolism), Mice, Inbred C57BL, Mice, Knockout, Neurons (physiology), Nitriles, Paraventricular Hypothalamic Nucleus (physiology), Propionates, Protein Kinase C-delta (metabolism), Signal Transduction, Type C Phospholipases (metabolism).
- MESH :
- chemical , metabolism : Anilides, Cyclic AMP-Dependent Protein Kinases, GTP-Binding Protein alpha Subunits, Gq-G11, Protein Kinase C-delta, Type C Phospholipases.
- chemical , physiology : Estradiol.
- chemical : Acrylamides, Corticotropin-Releasing Hormone, Nitriles, Propionates.
- physiology : Neurons, Paraventricular Hypothalamic Nucleus.
- Animals, Excitatory Postsynaptic Potentials, Female, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction.
Abstract
CRH neurons in the hypothalamic paraventricular nucleus (PVN) play a central role in regulating the hypothalamus-pituitary-adrenal (HPA) axis and are directly influenced by 17β-estradiol (E2). Although compelling evidence has suggested the existence of membrane-associated estrogen receptors (mERs) in hypothalamic and other central nervous system neurons, it remains unknown whether E2 impacts CRH neuronal excitability through this mechanism. The purpose of the current study is to examine the existence and function of mER signaling in PVN CRH neurons. Whole-cell recordings were made from CRH neurons identified by Alexa Fluor 594 labeling and post hoc immunostaining in ovariectomized female mice. E2 (100nM) rapidly suppressed the M-current (a voltage-dependent K(+) current) and potentiated glutamatergic excitatory postsynaptic currents. The putative Gq-coupled mER (Gq-mER) characterized in hypothalamic proopiomelanocortin neurons initiates a phospholipase C-protein kinase C-protein kinase A pathway; therefore, we examined the involvement of this pathway using selective inhibitors. Indeed, the ER antagonist ICI 182780 and inhibitors of Gq-phospholipase C-protein kinase C-protein kinase A blocked E2's actions, suggesting dependence on the Gq-mER. Furthermore, STX, a selective ligand for the Gq-mER, mimicked E2's actions. Finally, to examine the in vivo effect of Gq-mER activation, E2 or STX injection increased c-fos expression in CRH neurons in the PVN, suggesting CRH neuronal activation. This corresponded to an increase in plasma corticosterone. We conclude that the Gq-mER plays a critical role in the rapid regulation of CRH neuronal activity and the HPA axis. Our findings provide a potential underlying mechanism for E2's involvement in the pathophysiology of HPA-associated mood disorders.
DOI: 10.1210/en.2016-1191
PubMed: 27387482
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice.</title><author><name sortKey="Hu, Pu" sort="Hu, Pu" uniqKey="Hu P" first="Pu" last="Hu">Pu Hu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Ji" sort="Liu, Ji" uniqKey="Liu J" first="Ji" last="Liu">Ji Liu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Yasrebi, Ali" sort="Yasrebi, Ali" uniqKey="Yasrebi A" first="Ali" last="Yasrebi">Ali Yasrebi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Gotthardt, Juliet D" sort="Gotthardt, Juliet D" uniqKey="Gotthardt J" first="Juliet D" last="Gotthardt">Juliet D. Gotthardt</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Bello, Nicholas T" sort="Bello, Nicholas T" uniqKey="Bello N" first="Nicholas T" last="Bello">Nicholas T. 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Pang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Roepke, Troy A" sort="Roepke, Troy A" uniqKey="Roepke T" first="Troy A" last="Roepke">Troy A. Roepke</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27387482</idno><idno type="pmid">27387482</idno><idno type="doi">10.1210/en.2016-1191</idno><idno type="wicri:Area/PubMed/Corpus">001055</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001055</idno><idno type="wicri:Area/PubMed/Curation">001055</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001055</idno><idno type="wicri:Area/PubMed/Checkpoint">001082</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001082</idno><idno type="wicri:Area/Ncbi/Merge">001691</idno><idno type="wicri:Area/Ncbi/Curation">001691</idno><idno type="wicri:Area/Ncbi/Checkpoint">001691</idno><idno type="wicri:Area/Main/Merge">001233</idno><idno type="wicri:Area/Main/Curation">001229</idno><idno type="wicri:Area/Main/Exploration">001229</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice.</title><author><name sortKey="Hu, Pu" sort="Hu, Pu" uniqKey="Hu P" first="Pu" last="Hu">Pu Hu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Ji" sort="Liu, Ji" uniqKey="Liu J" first="Ji" last="Liu">Ji Liu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Yasrebi, Ali" sort="Yasrebi, Ali" uniqKey="Yasrebi A" first="Ali" last="Yasrebi">Ali Yasrebi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Gotthardt, Juliet D" sort="Gotthardt, Juliet D" uniqKey="Gotthardt J" first="Juliet D" last="Gotthardt">Juliet D. Gotthardt</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Bello, Nicholas T" sort="Bello, Nicholas T" uniqKey="Bello N" first="Nicholas T" last="Bello">Nicholas T. Bello</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Pang, Zhiping P" sort="Pang, Zhiping P" uniqKey="Pang Z" first="Zhiping P" last="Pang">Zhiping P. Pang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author><author><name sortKey="Roepke, Troy A" sort="Roepke, Troy A" uniqKey="Roepke T" first="Troy A" last="Roepke">Troy A. Roepke</name><affiliation wicri:level="2"><nlm:affiliation>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Department of Animal Sciences (P.H., A.Y., J.D.G., N.T.B., T.A.R.), School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, and Child Health Institute of New Jersey (J.L., Z.P.P.) and Department of Neuroscience and Cell Biology (J.L., Z.P.P.), Rutgers Robert Wood Johnson Medical School, New Brunswick</wicri:cityArea></affiliation></author></analytic><series><title level="j">Endocrinology</title><idno type="eISSN">1945-7170</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acrylamides</term><term>Anilides (metabolism)</term><term>Animals</term><term>Corticotropin-Releasing Hormone</term><term>Cyclic AMP-Dependent Protein Kinases (metabolism)</term><term>Estradiol (physiology)</term><term>Excitatory Postsynaptic Potentials</term><term>Female</term><term>GTP-Binding Protein alpha Subunits, Gq-G11 (metabolism)</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Neurons (physiology)</term><term>Nitriles</term><term>Paraventricular Hypothalamic Nucleus (physiology)</term><term>Propionates</term><term>Protein Kinase C-delta (metabolism)</term><term>Signal Transduction</term><term>Type C Phospholipases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acrylamides</term><term>Anilides (métabolisme)</term><term>Animaux</term><term>Corticolibérine</term><term>Cyclic AMP-Dependent Protein Kinases (métabolisme)</term><term>Femelle</term><term>Neurones (physiologie)</term><term>Nitriles</term><term>Noyau paraventriculaire de l'hypothalamus (physiologie)</term><term>Oestradiol (physiologie)</term><term>Potentiels post-synaptiques excitateurs</term><term>Propionates</term><term>Protein kinase C-delta (métabolisme)</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Sous-unités alpha Gq-G11 des protéines G (métabolisme)</term><term>Transduction du signal</term><term>Type C Phospholipases (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Anilides</term><term>Cyclic AMP-Dependent Protein Kinases</term><term>GTP-Binding Protein alpha Subunits, Gq-G11</term><term>Protein Kinase C-delta</term><term>Type C Phospholipases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Estradiol</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Acrylamides</term><term>Corticotropin-Releasing Hormone</term><term>Nitriles</term><term>Propionates</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Anilides</term><term>Cyclic AMP-Dependent Protein Kinases</term><term>Protein kinase C-delta</term><term>Sous-unités alpha Gq-G11 des protéines G</term><term>Type C Phospholipases</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Neurones</term><term>Noyau paraventriculaire de l'hypothalamus</term><term>Oestradiol</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Neurons</term><term>Paraventricular Hypothalamic Nucleus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Excitatory Postsynaptic Potentials</term><term>Female</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Acrylamides</term><term>Animaux</term><term>Corticolibérine</term><term>Femelle</term><term>Nitriles</term><term>Potentiels post-synaptiques excitateurs</term><term>Propionates</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">CRH neurons in the hypothalamic paraventricular nucleus (PVN) play a central role in regulating the hypothalamus-pituitary-adrenal (HPA) axis and are directly influenced by 17β-estradiol (E2). Although compelling evidence has suggested the existence of membrane-associated estrogen receptors (mERs) in hypothalamic and other central nervous system neurons, it remains unknown whether E2 impacts CRH neuronal excitability through this mechanism. The purpose of the current study is to examine the existence and function of mER signaling in PVN CRH neurons. Whole-cell recordings were made from CRH neurons identified by Alexa Fluor 594 labeling and post hoc immunostaining in ovariectomized female mice. E2 (100nM) rapidly suppressed the M-current (a voltage-dependent K(+) current) and potentiated glutamatergic excitatory postsynaptic currents. The putative Gq-coupled mER (Gq-mER) characterized in hypothalamic proopiomelanocortin neurons initiates a phospholipase C-protein kinase C-protein kinase A pathway; therefore, we examined the involvement of this pathway using selective inhibitors. Indeed, the ER antagonist ICI 182780 and inhibitors of Gq-phospholipase C-protein kinase C-protein kinase A blocked E2's actions, suggesting dependence on the Gq-mER. Furthermore, STX, a selective ligand for the Gq-mER, mimicked E2's actions. Finally, to examine the in vivo effect of Gq-mER activation, E2 or STX injection increased c-fos expression in CRH neurons in the PVN, suggesting CRH neuronal activation. This corresponded to an increase in plasma corticosterone. We conclude that the Gq-mER plays a critical role in the rapid regulation of CRH neuronal activity and the HPA axis. Our findings provide a potential underlying mechanism for E2's involvement in the pathophysiology of HPA-associated mood disorders.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>New Jersey</li></region></list><tree><country name="États-Unis"><region name="New Jersey"><name sortKey="Hu, Pu" sort="Hu, Pu" uniqKey="Hu P" first="Pu" last="Hu">Pu Hu</name></region><name sortKey="Bello, Nicholas T" sort="Bello, Nicholas T" uniqKey="Bello N" first="Nicholas T" last="Bello">Nicholas T. Bello</name><name sortKey="Gotthardt, Juliet D" sort="Gotthardt, Juliet D" uniqKey="Gotthardt J" first="Juliet D" last="Gotthardt">Juliet D. Gotthardt</name><name sortKey="Liu, Ji" sort="Liu, Ji" uniqKey="Liu J" first="Ji" last="Liu">Ji Liu</name><name sortKey="Pang, Zhiping P" sort="Pang, Zhiping P" uniqKey="Pang Z" first="Zhiping P" last="Pang">Zhiping P. Pang</name><name sortKey="Roepke, Troy A" sort="Roepke, Troy A" uniqKey="Roepke T" first="Troy A" last="Roepke">Troy A. Roepke</name><name sortKey="Yasrebi, Ali" sort="Yasrebi, Ali" uniqKey="Yasrebi A" first="Ali" last="Yasrebi">Ali Yasrebi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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