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Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice

Descriptive

TypeOfResource
Text
TitleInfo
Title
Gq Protein-Coupled Membrane-Initiated Estrogen Signaling Rapidly Excites Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus in Female Mice
Identifier (type = pmcid)
PMC5007888
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Animal Sciences
Name (authority = RutgersOrg-School); (type = corporate)
NamePart
School of Environmental and Biological Sciences (SEBS)
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Neuroscience and Cell Biology
Name (authority = RutgersOrg-Department); (type = corporate)
NamePart
Child Health Institute of New Jersey (CHINJ)
Name (authority = RutgersOrg-School); (type = corporate)
NamePart
Robert Wood Johnson Medical School (RWJMS)
Genre (authority = RULIB-FS)
Article, Refereed
Genre (authority = NISO JAV)
Accepted Manuscript (AM)
Note (type = peerReview)
Peer reviewed
OriginInfo
DateIssued (encoding = w3cdtf); (keyDate = yes)
2016
Abstract (type = 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.
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
PhysicalDescription
InternetMediaType
application/pdf
Extent
40 p.
Extension
DescriptiveEvent
Type
Citation
DateTime (encoding = w3cdtf)
2016
AssociatedObject
Name
Endocrinology
Type
Journal
Relationship
Has part
Detail
3604-3620
Identifier (type = volume and issue)
157(9)
Reference (type = url)
http://dx.doi.org/10.1210/en.2016-1191
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
National Institutes of Health
AssociatedEntity
Role
Originator
Name
Troy A Roepke
AssociatedObject
Type
Grant number
Name
R00DK083457
Subject (authority = local)
Topic
Signal transduction
Subject (authority = local)
Topic
Hypothalamus
Subject (authority = local)
Topic
Tissue membrane
Subject (authority = local)
Topic
Neurons
Subject (authority = local)
Topic
Paraventricular nucleus
Subject (authority = local)
Topic
Plasma
Subject (authority = local)
Topic
Mice
Subject (authority = local)
Topic
Mertk gene
Name (type = personal)
NamePart (type = family)
Hu
NamePart (type = given)
Pu
Affiliation
Animal Sciences, Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Liu
NamePart (type = given)
Ji
Affiliation
Neuroscience and Cell Biology; Child Health Institute of New Jersey (CHINJ)
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Yasrebi
NamePart (type = given)
Ali
Affiliation
Animal Sciences, Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Gotthardt
NamePart (type = given)
Juliet D.
Affiliation
Animal Sciences, Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Bello
NamePart (type = given)
Nicholas T.
Affiliation
Animal Sciences, Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (type = personal)
NamePart (type = family)
Pang
NamePart (type = given)
Zhiping
Affiliation
Neuroscience and Cell Biology; Child Health Institute of New Jersey (CHINJ)
Role
RoleTerm (authority = marcrt); (type = text)
author
Name (authority = orcid); (authorityURI = http://id.loc.gov/vocabulary/identifiers/orcid.html); (type = personal); (valueURI = http://orcid.org/0000-0001-5426-2266)
NamePart (type = family)
Roepke
NamePart (type = given)
Troy A.
Affiliation
Animal Sciences, Rutgers University
Role
RoleTerm (authority = marcrt); (type = text)
author
RelatedItem (type = host)
TitleInfo
Title
Roepke, Troy A.
Identifier (type = local)
rucore30176800001
RelatedItem (type = host)
TitleInfo
Title
Liu, Ji
Identifier (type = local)
rucore30223600001
RelatedItem (type = host)
TitleInfo
Title
Yasrebi, Ali
Identifier (type = local)
rucore30190700001
RelatedItem (type = host)
TitleInfo
Title
Gotthardt, Juliet D.
Identifier (type = local)
rucore30190400001
RelatedItem (type = host)
TitleInfo
Title
Bello, Nicholas T.
Identifier (type = local)
rucore30190300001
RelatedItem (type = host)
TitleInfo
Title
Pang, Zhiping
Identifier (type = local)
rucore30223800001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T32Z17W9
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Copyright
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Availability
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Reason
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RightsEvent
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AssociatedObject
Type
License
Name
Multiple author license v. 1
Detail
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1.6
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2016-06-30T14:50:58
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2017-02-13T18:13:28
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