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    • Graduate School - MU Theses and Dissertations (MU)
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    • 2007 MU theses - Freely available online
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    The effects of the selective estrogen receptor modulators MPP and raloxifene in normal and cancerous human and murine uterine tissue

    Davis, Angela Marie
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    [PDF] research.pdf (3.057Mb)
    Date
    2007
    Format
    Thesis
    Metadata
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    Abstract
    The goal of this research was to determine the in vitro and in vivo effects of the Selective Estrogen Receptor Modulators (SERMs), methyl-piperidino-pyrazole (MPP), raloxifene, ICI 182,780 and 17[beta]-estradiol on endometrial carcinoma cells in culture and on murine uterine tissue. These SERMs have been developed to target and understand the role of estrogen receptor action in estrogen-responsive organs. Based on their antagonistic actions, SERMs have both real and potential value in treating estrogen-responsive cancers, including endometrial cancer. The studies described herein verify that the SERMs MPP and raloxifene demonstrate partial agonistic effects in ovariectomized wild-type and ER-[beta] knockout (ER[beta]KO) mice but also induce apoptosis and proliferation in vitro in cultured endometrial cell lines, Ishikawa and RL-95. Thus, MPP and raloxifene exert apparently contrasting in vitro and in vivo effects due to their mixed agonist/antagonist action on murine uterine estrogen receptor in vivo. In addition to these data, I report gene expression changes in the uterus of mice treated individually or with the combination of 17[beta]-estradiol and the SERMs, MPP, raloxifene, ICI 182,780 are reported herein. A greater number of genes showed up- or down regulation when the mice were co-treated with estrogen and one of the SERMs than when dosed with one of the compounds alone. A combination of a SERM and 17[beta]-estradiol resulted in a combinatorial or synergistic effect. These data may be explained by the fact that dual administration of a SERM with [beta]-estradiol allows the compounds to bind combinatorially to heterodimers as well as homdimers of the two receptors ER[alpha] and ER[beta]. These studies provide a framework of how 17[beta]-estradiol and various SERMs act in the uterus and might result in future therapies for gynecological maladies, including endometrial cancer.
    URI
    https://hdl.handle.net/10355/4999
    https://doi.org/10.32469/10355/4999
    Degree
    M.S.
    Thesis Department
    Animal sciences (MU)
    Collections
    • Animal Sciences electronic theses and dissertations (MU)
    • 2007 MU theses - Freely available online

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