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Estradiol, MCH and Food Intake

Title: Estradiol, MCH and Food Intake.
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Name(s): Santollo, Jessica, 1982-, author
Eckel, Lisa A., professor directing dissertation
Bass, Hank, university representative
Overton, J. Michael, committee member
Taylor, Jeanette, committee member
Wang, Zuoxin, committee member
Department of Psychology, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2010
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: While it is well established that estradiol exerts a potent, anorexigenic effect in a variety of species (27; 33; 57; 84), the mechanism underlying this action of estradiol is poorly understood. My previous research has demonstrated that the orexigenic strength of melanin concentrating hormone (MCH) is decreased by estradiol. For example, males and diestrous females are more sensitive to the orexigenic effect of MCH compared to estrous females, and MCH-induced feeding is decreased by estradiol treatment in ovariectomized (OVX) rats (65; 93). The goal of this dissertation was to examine whether estradiol's anorexigenic effect is mediated, in part, by its ability to decrease MCH signaling. MCH is a hypothalamic neuropeptide that is most recognized for its robust orexigenic action in mammals (1; 17; 26; 83). Estradiol binds to the ERá nuclear receptor to influence genes involved in the controls of food intake (88; 94; 95; 104). Because nuclear estrogen receptors (ERs) are capable of inducing or repressing gene transcription, there are multiple mechanisms by which estradiol could influence the MCH system. For example, estradiol may decrease MCH synthesis and/or the number of MCH receptors (MCHR1s). To examine these hypotheses, brain tissue sections, obtained at different stages of the estrous cycle, were processed for MCH and MCHR1 protein expression. Increased serum estradiol levels were associated with a decrease in MCH and MCHR1 protein expression in the hypothalamus of cycling rats. In order to determine whether the changes in MCH protein expression across the estrous cycle were caused by fluctuations in estradiol levels, we conducted a similar study in which estradiol levels were directly manipulated in OVX rats. Administration of both estradiol and a drug that selectively targets ERá significantly reduced MCH and MCHR1 expression in the hypothalamus. This is an important finding because it provides the first demonstration that endogenous estradiol acts via ERá to decrease MCH and MCHR1 protein expression. Next, to determine if changes in protein expression were caused by a direct effect of estradiol at the level of the MCH and MCHR1 gene, MCH and MCHR1 gene expression was examined in a neuronal hypothalamic cell line. Surprisingly, estradiol failed to alter either MCH or MCHR1 gene expression. In further support of this finding, we demonstrated that MCH and ERá are both expressed in the lateral hypothalamus (LH) and zona incerta (ZI) of female rats, however, they are not co-localized within the same neurons. These two findings suggest that the earlier observations of decreased MCH and MCHR1 protein expression are mediated by an indirect action of estradiol. Finally, we tested whether the ERs in the LH are one possible site responsible for inhibiting the orexigenic strength of the MCH system. To do so we delivered estradiol directly into the LH and found that it failed to influence food intake. These studies demonstrate that estradiol is capable of inhibiting the MCH system by decreasing synthesis of both MCH and MCHR1 protein, however, estradiol likely causes such changes by an indirect mechanism that does not involve the LH.
Identifier: FSU_migr_etd-2081 (IID)
Submitted Note: A Dissertation Submitted to the Department of Psychology in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy.
Degree Awarded: Fall Semester, 2010.
Date of Defense: July 23, 2010.
Keywords: Estrogen, Hormones, Orexigenic
Bibliography Note: Includes bibliographical references.
Advisory Committee: Lisa A. Eckel, Professor Directing Dissertation; Hank Bass, University Representative; J. Michael Overton, Committee Member; Jeanette Taylor, Committee Member; Zuoxin Wang, Committee Member.
Subject(s): Psychology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_etd-2081
Owner Institution: FSU

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Santollo, J. (2010). Estradiol, MCH and Food Intake. Retrieved from http://purl.flvc.org/fsu/fd/FSU_migr_etd-2081