Staff View
Enterohepatic nuclear receptor signaling during pregnancy

Descriptive

TitleInfo
Title
Enterohepatic nuclear receptor signaling during pregnancy
Name (type = personal)
NamePart (type = family)
Moscovitz
NamePart (type = given)
Jamie Esther
NamePart (type = date)
1989-
DisplayForm
Jamie Esther Moscovitz
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Aleksunes
NamePart (type = given)
Lauren M
DisplayForm
Lauren M Aleksunes
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Guo
NamePart (type = given)
Grace L
DisplayForm
Grace L Guo
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Roepke
NamePart (type = given)
Troy
DisplayForm
Troy Roepke
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Gallo
NamePart (type = given)
Michael
DisplayForm
Michael Gallo
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Thompson
NamePart (type = given)
Kary
DisplayForm
Kary Thompson
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2016
DateOther (qualifier = exact); (type = degree)
2016-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2016
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Physiological adaptations to the intestine-liver axis during pregnancy alter the disposition of xenobiotics and endobiotics. As a result, some pregnant women experience decreased efficacy or adverse reactions to prescription medications (xenobiotic effect), while others may become susceptible to cholestatic liver disease due to enhanced bile acid levels (endobiotic effect). The purpose of this dissertation research was to characterize molecular adaptations in enterohepatic nuclear receptor signaling and downstream bile acid and xenobiotic disposition pathways that can occur during late pregnancy. In ilea collected from mice in late gestation, an overall down-regulation of Farnesoid X Receptor (Fxr/Nr1h4) and Pregnane X Receptor (Pxr/Nr1i2) signaling, including target enzyme and transporter expression, was observed. To explore potential mechanisms, the ability of candidate sex hormones to alter the expression of enzyme and transport genes regulated by FXR and PXR were studied in human intestinal cells. In vitro studies suggest a prominent role for progesterone-mediated interference with PXR signaling in the intestine during pregnancy that could contribute to altered xenobiotic transport. Further assessment of the ability of activated Fxr to modulate hepatic and intestinal regulation of bile acid synthesis and transport pathways during pregnancy was investigated in mice. Treatment of pregnant mice with the specific Fxr agonist GW4064 restored the expression of bile acid synthesis enzymes and transporters towards levels typically observed in virgin mice. This study provides the molecular basis for a novel approach to restore bile acid homeostasis in patients with maternal cholestasis. Finally, loss-of-function studies in pregnant Fxr-null mice revealed that deficiency in the Fxr gene prevents pregnancy-mediated repression of key bile acid regulatory factors and transporters, largely in the intestines. Taken together, these data advance our understanding of alterations in chemical disposition during pregnancy, and the overall “procholestatic” state of pregnancy that sensitizes women to acquiring liver disease.
Subject (authority = RUETD)
Topic
Toxicology
Subject (authority = ETD-LCSH)
Topic
Pregnancy
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_7471
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xvi, 248 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Jamie Esther Moscovitz
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3TM7DF6
Genre (authority = ExL-Esploro)
ETD doctoral
Back to the top

Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Moscovitz
GivenName
Jamie
MiddleName
Esther
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-08-09 11:50:18
AssociatedEntity
Name
Jamie Moscovitz
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
Back to the top

Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
CreatingApplication
Version
1.5
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2016-08-09T11:36:55
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2016-08-09T11:36:55
ApplicationName
Microsoft® Word 2010
Back to the top
Version 8.5.5
Rutgers University Libraries - Copyright ©2024