dc.contributor.advisor | Rosenfeld, Cheryl S. | eng |
dc.contributor.advisor | Roberts, R. M. (Robert Michael), 1940- | eng |
dc.contributor.author | Davis, Angela Marie | eng |
dc.date.issued | 2007 | eng |
dc.date.submitted | 2007 Fall | eng |
dc.description | The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. | eng |
dc.description | Title from title screen of research.pdf file (viewed on March 21, 2008) | eng |
dc.description | Includes bibliographical references. | eng |
dc.description | Thesis (M.S.) University of Missouri-Columbia 2007. | eng |
dc.description | Dissertations, Academic -- University of Missouri--Columbia -- Animal sciences. | eng |
dc.description.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. | eng |
dc.identifier.merlin | b6277539x | eng |
dc.identifier.oclc | 213814888 | eng |
dc.identifier.uri | https://hdl.handle.net/10355/4999 | |
dc.identifier.uri | https://doi.org/10.32469/10355/4999 | eng |
dc.language | English | eng |
dc.publisher | University of Missouri--Columbia | eng |
dc.relation.ispartofcommunity | University of Missouri--Columbia. Graduate School. Theses and Dissertations | eng |
dc.subject | methyl-piperidino-pyrazole. | eng |
dc.subject | methyl-piperidino-pyrazole | eng |
dc.subject.lcsh | Selective estrogen receptor modulators | eng |
dc.subject.lcsh | Raloxifene | eng |
dc.subject.lcsh | Generative organs, Female -- Diseases | eng |
dc.subject.lcsh | Estrogen | eng |
dc.subject.lcsh | Cancer cells | eng |
dc.title | The effects of the selective estrogen receptor modulators MPP and raloxifene in normal and cancerous human and murine uterine tissue | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Animal sciences (MU) | eng |
thesis.degree.grantor | University of Missouri--Columbia | eng |
thesis.degree.level | Masters | eng |
thesis.degree.name | M.S. | eng |