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Arcuate ER alpha-mediated estrogen signaling pathways and regulation of KNDy-associated gene expression in female mice

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Title
Arcuate ER alpha-mediated estrogen signaling pathways and regulation of KNDy-associated gene expression in female mice
Name (type = personal)
NamePart (type = family)
Yang
NamePart (type = given)
Jennifer A.
NamePart (type = date)
1989-
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Jennifer A. Yang
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author
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Troy A
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Troy A Roepke
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Advisory Committee
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chair
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Bagnell
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Carol
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Carol Bagnell
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Advisory Committee
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internal member
Name (type = personal)
NamePart (type = family)
John-Alder
NamePart (type = given)
Henry
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Henry John-Alder
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Advisory Committee
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internal member
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Pang
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Zhiping
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Zhiping Pang
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Advisory Committee
Role
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outside member
Name (type = corporate)
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Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
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Text
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theses
OriginInfo
DateCreated (qualifier = exact)
2016
DateOther (qualifier = exact); (type = degree)
2016-10
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2016
Place
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xx
Language
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eng
Abstract (type = abstract)
Central signaling of 17β-estradiol (E2) in the arcuate nucleus (ARC) is important in many homeostatic functions including reproduction, energy balance, and thermoregulation, among others. KNDy neurons that coexpress kisspeptin, neurokinin B, and dynorphin function in control of multiple homeostatic functions and are integrators of reproduction and energy balance. In this dissertation, I characterize ER-mediated and ER-independent signaling in the ARC and identify the impact of energy balance and E2 on KNDy neurons. First, I characterize ER-mediated E2 signaling in the ARC, where E2 binds to estrogen receptor-alpha (ERα), translocates to the nucleus, and regulates gene transcription by binding to the Estrogen Response Element (ERE) on DNA through ERE-independent signaling. However, E2 also functions through ERE-independent signaling, such as interacting with nuclear transcription factors and binding to E2- responsive G-protein coupled receptors. I use three genotypes of mice: 1) wild-type, 2) knock in/knock out (KIKO), which lack ERE-dependent signaling, and 3) ERα total knock out (ERKO) to determine differential E2 signaling in the ARC. I found that multiple genes involved in reproduction and energy balance are controlled by E2 through ERE- dependent and ERE-independent mechanisms and identify novel signaling pathways that are modulated by E2. In the last section, I examined the interactions of E2 and energy balance on KNDy-associated gene expression in the ARC. I determined that in overnutrition and undernutrition, ARC expression of KNDy neuropeptides and receptors is disrupted, leading to downstream changes in gonadotropin (LH and FSH) production. Our previous studies found that in NPY/AgRP neurons, E2 interacted with fasting and diet-induced obesity to regulate genes involved in ghrelin signaling. Overnutrition and undernutrition did not regulate these ghrelin signaling genes in Tac2 neurons. However, E2 augments the expression of growth hormone secretagogue receptor (Ghsr), ghrelin’s receptor, in Tac2 neurons by six- to eight-fold, suggesting that E2 modulates ghrelin signaling in KNDy neurons. In summary, our results suggest differential E2 signaling mechanisms in the ARC are important to maintain energy homeostasis and reproduction and that expression of KNDy genes are regulated by both positive and negative energy balance, leading to downstream changes in reproduction.
Subject (authority = RUETD)
Topic
Endocrinology and Animal Biosciences
Subject (authority = ETD-LCSH)
Topic
Estrogen
RelatedItem (type = host)
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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ETD_7479
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (xi, 213 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Jennifer A. Yang
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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Identifier (type = doi)
doi:10.7282/T3VT1VD7
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Yang
GivenName
Jennifer
MiddleName
A.
Role
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RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-08-10 20:56:46
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Jennifer Yang
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Affiliation
Rutgers University. Graduate School - New Brunswick
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2018-10-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2018.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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