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Tamoxifen-Mediated Changes in Estrog...

Misquez, Amanda Marie.

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Tamoxifen-Mediated Changes in Estrogen-Dependent Gene Expression in Hypothalamic Neurons Responsible for Hot Flashes.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Tamoxifen-Mediated Changes in Estrogen-Dependent Gene Expression in Hypothalamic Neurons Responsible for Hot Flashes./
Author:	Misquez, Amanda Marie.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
Description:	62 p.
Notes:	Source: Masters Abstracts International, Volume: 84-12.
Contained By:	Masters Abstracts International84-12.
Subject:	Physiology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30528564
ISBN:	9798379719524

Tamoxifen-Mediated Changes in Estrogen-Dependent Gene Expression in Hypothalamic Neurons Responsible for Hot Flashes.
Misquez, Amanda Marie.

Tamoxifen-Mediated Changes in Estrogen-Dependent Gene Expression in Hypothalamic Neurons Responsible for Hot Flashes. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 62 p.

Source: Masters Abstracts International, Volume: 84-12.

Thesis (M.S.)--University of California, Los Angeles, 2023.

Tamoxifen (Tmx) is a selective estrogen receptor modulator widely used as a chemotherapeutic drug in the treatment regimen for estrogen-sensitive breast cancer. Tmx treatment leads to many side effects; the most prominently reported side effect is hot flashes. Hot flashes are episodes of thermodysregulation and have been shown to be caused by estrogen-receptor {CE}{lstrok} (ER{CE}{lstrok}) signaling in the hypothalamus. In this thesis, we delivered a custom, bi-functional fluorescent reporter to three estrogen-sensitive nuclei in the hypothalamus that regulate body temperature: the medial preoptic area (MPA), the arcuate nucleus (ARC), and the ventrolateral region of the ventromedial hypothalamus (VMHvl). The reporter labels estrogen-sensitive neurons that express ER{CE}{lstrok} and reports whether neurons alter estrogen-dependent gene transcription and expression in response to Tmx treatment. Upon delivering the fluorescent reporter to the three thermoregulatory and estrogen-sensitive regions of interest (the MPA, ARC, and VMHvl), we observed that Tmx treatment in Esr1 Cre and Kiss1 Cre mice showed no significant differences in ERE-dependent gene expression in the MPA, ARC, and VMHvl compared to control, Oil-treated mice. Therefore, we are unable to detect Tmx-induced changes in gene expression in estrogen-sensitive neurons of the MPA, ARC, or VMHvl. We conclude that Tmx does not alter estrogen-dependent gene expression in the hypothalamus under the conditions we used. As our Tamoxifen treatment paradigm is sufficient to induce thermodysregulation, this implies the intriguing possibility that Tamoxifen induces hot flashes without widespread changes in hypothalamic gene expression.{A0}

ISBN: 9798379719524Subjects--Topical Terms:

518431
Physiology.
Subjects--Index Terms:

Arcuate nucleus

Tamoxifen-Mediated Changes in Estrogen-Dependent Gene Expression in Hypothalamic Neurons Responsible for Hot Flashes.
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502 $a Thesis (M.S.)--University of California, Los Angeles, 2023.
520 $a Tamoxifen (Tmx) is a selective estrogen receptor modulator widely used as a chemotherapeutic drug in the treatment regimen for estrogen-sensitive breast cancer. Tmx treatment leads to many side effects; the most prominently reported side effect is hot flashes. Hot flashes are episodes of thermodysregulation and have been shown to be caused by estrogen-receptor {CE}{lstrok} (ER{CE}{lstrok}) signaling in the hypothalamus. In this thesis, we delivered a custom, bi-functional fluorescent reporter to three estrogen-sensitive nuclei in the hypothalamus that regulate body temperature: the medial preoptic area (MPA), the arcuate nucleus (ARC), and the ventrolateral region of the ventromedial hypothalamus (VMHvl). The reporter labels estrogen-sensitive neurons that express ER{CE}{lstrok} and reports whether neurons alter estrogen-dependent gene transcription and expression in response to Tmx treatment. Upon delivering the fluorescent reporter to the three thermoregulatory and estrogen-sensitive regions of interest (the MPA, ARC, and VMHvl), we observed that Tmx treatment in Esr1 Cre and Kiss1 Cre mice showed no significant differences in ERE-dependent gene expression in the MPA, ARC, and VMHvl compared to control, Oil-treated mice. Therefore, we are unable to detect Tmx-induced changes in gene expression in estrogen-sensitive neurons of the MPA, ARC, or VMHvl. We conclude that Tmx does not alter estrogen-dependent gene expression in the hypothalamus under the conditions we used. As our Tamoxifen treatment paradigm is sufficient to induce thermodysregulation, this implies the intriguing possibility that Tamoxifen induces hot flashes without widespread changes in hypothalamic gene expression.{A0}
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