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Effects of methoxychlor in ovarian granulosa cell in vitro
Descriptive
TitleInfo
Title
Effects of methoxychlor in ovarian granulosa cell in vitro
Name
(type = personal)
NamePart
(type = family)
Harvey
NamePart
(type = given)
Craig Nicholas
NamePart
(type = date)
1978-
DisplayForm
Craig Harvey
Role
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(authority = RULIB)
author
Name
(type = personal)
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(type = family)
Zarbl
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Helmut
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Helmut Zarbl
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Advisory Committee
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(authority = RULIB)
chair
Name
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NamePart
(type = family)
Uzumcu
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Mehmet
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Mehmet Uzumcu
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Advisory Committee
Role
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(authority = RULIB)
co-chair
Name
(type = personal)
NamePart
(type = family)
White
NamePart
(type = given)
Lori A
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Lori A White
Affiliation
Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Buckley
NamePart
(type = given)
Brian
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Brian Buckley
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Zachow
NamePart
(type = given)
Rob
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Rob Zachow
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
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(authority = RULIB)
school
TypeOfResource
Text
Genre
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theses
OriginInfo
DateCreated
(qualifier = exact)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-10
CopyrightDate
(qualifier = exact)
2012
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Methoxychlor (MXC) has been shown to alter ovarian folliculogenesis through inhibition of granulosa cell steroidogenesis, which is required for normal reproductive physiology. The process of granulosa cell differentiation requires estrogen to augment follicle-stimulating hormone (FSH) activity and the ovulatory response to gonadotropins. This dissertation focuses on the effect of methoxychlor, which is suspected of acting through its metabolite, 2,2-bis-(p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE), on granulosa cell function. HPTE acts as an estrogen receptor α agonist and an estrogen receptor β antagonist. The well characterized immature rat granulosa cell model was used to generate samples for analysis of intracellular cAMP, protein, and gene expression. The transcriptional responses induced by MXC and HPTE were investigated using Affymetrix microarray Rat Genome 230 2.0. Alterations in guanine nucleotide binding protein-coupled receptors (GPCRs) signaling were suggested to be affected by MXC and HPTE. G-protein coupled receptors (e.g. FSH and LHR) are among the most common and successful drug targets produced by pharmaceutical companies and are critical to granulosa cell differentiation. Recent reports suggest that estrogen receptor β is required for FSH-induced granulosa cell differentiation, response to gonadotropins (i.e., LHR) in the pre-ovulatory follicle, and maximal cAMP production. MXC and HPTE reduced FSH-mediated LHR expression and cAMP levels. Our results using two estrogen receptor β antagonists, ICI 182,780 (fulvestrant or falsodex) and 4-[2-phenyl-5,7-bis (tri-fluoro-methyl) pyrazolo [1,5-a]pyrimidin-3-yl] phenol (PTHPP) support an association between estrogen receptor expression β and cAMP. However, co-treatment of granulosa cells with an estrogen receptor β agonist, diarylpropionitrile (DPN), did not reverse the effect of HPTE on cAMP. While there are clear differences in the morphology of FSH-stimulated granulosa cells treated with HPTE and MXC, as well as production of estradiol 17β (E2) when compared to FSH-alone, the use of dibutyryl cAMP (dbcAMP) was protective against the effects of MXC and HPTE on gene expression and steroidogenesis. Furthermore, MXC and HPTE suppressed estrogen signaling through inhibition of estrogen receptor expression and E2 production. We showed that cell viability was unaffected by MXC or HPTE at high doses, but MXC and HPTE did induce significant changes in gene expression and pathway activity.
Subject
(authority = RUETD)
Topic
Toxicology
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
Identifier
ETD_4127
PhysicalDescription
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electronic resource
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application/pdf
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text/xml
Extent
xiv, 217 p. : ill.
Note
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Ph.D.
Note
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Includes bibliographical references
Note
(type = statement of responsibility)
by Craig Nicholas Harvey
Subject
(authority = ETD-LCSH)
Topic
Methoxychlor--Toxicology
Subject
(authority = ETD-LCSH)
Topic
Ovaries--Abnormalities
Subject
(authority = ETD-LCSH)
Topic
Cytology--Research
Identifier
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http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066758
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T30K273Z
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Harvey
GivenName
Craig
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2012-05-25 13:27:26
AssociatedEntity
Name
Craig Harvey
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.
RightsEvent
DateTime
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2012-10-31
DateTime
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2013-05-02
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 2nd, 2013.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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4332544
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