Thesis (Ph.D.)--University of Delaware, 2009. / Principal faculty advisor: John T. Koh, Dept. of Chemistry & Biochemistry. Includes bibliographical references.

Thesis (M.Sc.)--College of William and Mary. / Vita. Includes bibliographical references. Also available via the World Wide Web.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1966. / Typescript. Vita. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--Wisconsin. / Includes bibliographical references (leaves 109-121).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Abstracted in Dissertation abstracts, v. 16 (1956) no. 11, p. 2034. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis--Wisconsin. / Vita. Includes bibliographical references.

Thesis (M. Med. Sc.)--University of Hong Kong, 2006.

Benign ovarian tumors and majority of epithelial ovarian cancers possess steroid receptors including estrogen receptors (ERs). However, the estrogen-ER signaling in ovarian carcinomas is not completely understood. Tumorigenesis is a multiple-step process involving dysregulated cell growth and metastasis. Tumor cells acquire the capacity of migration and invasion by temporal phenotypical and genotypical changes termed epithelial-mesenchymal transition (EMT). Considerable evidence implicates a mitogenic action of estrogen in early ovarian carcinogenesis. In contrast, its influence in the metastatic cascade of ovarian tumor cells remains obscure. In this study, I have focused on the role of 17β-estradiol (E2) in ovarian tumorigenesis. EMT related genes including E-cadherin, Snail, Slug, and Twist were examined. E2 treatment led to clear morphological changes and an enhanced cell migratory propensity. These morphologic and functional alterations were associated with changes in the abundance of EMT-related genes. Upon E2 stimulation, expression and promoter activity of the epithelial marker E-cadherin was strikingly suppressed, whereas EMT-associated transcription factors Snail and Slug were significantly up-regulated. This up-regulation was attributed to the increase in gene transcription activated by E2. Depletion of the endogenous Snail or Slug using small interfering RNA (siRNA) attenuated E2-mediated control in E-cadherin. In addition, the E2-induced cell migration was neutralized by Snail and Slug siRNAs, implying that both transcription factors are indispensable for the pro-metastatic actions of E2. Importantly, by using selective ER agonists as well as over-expression and siRNA approaches, it was identified that E2 triggered the metastatic behaviors exclusively through an ER⍺-dependent pathway. In contrast, overexpression of ERβ opposed the phenotypic changes and down-regulation of E-cadherin induced by ER⍺. In addition, microarray analysis was performed to characterize more putative downstream mediators of E2. Expression levels of 486 genes were found to be altered by at least 50% upon E2 treatment, and included several genes involved in oncogenesis, cell cycle control, apoptosis, signal transduction and the gene expression machinery. These candidate genes may be valuable for better delineating the ER pathways and functions. In summary, this study provides compelling arguments that estrogen can potentiate tumor progression by EMT induction, and highlight the crucial role of ER⍺ in ovarian tumorigenesis. / Medicine, Faculty of / Obstetrics and Gynaecology, Department of / Graduate

This project was undertaken to obtain more information about the nature of the water-soluble metabolites formed by rat liver since these had been shown to differ from the normal conjugates found in other species and are influenced by the sex of the animal and also by compounds in the soluble fraction of the cell. A comparison was made between these products and those formed from estrogens by mushroom phenolase under similar conditions, and it was found that glutathione had the same effect as the soluble fraction of the cell in increasing the yield of water-soluble metabolites in the rat liver microsomal system. This tripeptide also competed effectively with protein-binding and proposals to account for this reaction have been put forward. A marked increase in the yield of water-soluble estrogen derivatives was also observed when glutathione was added to the phenolase system, and although a different mechanism may be involved, similar types of products were formed. A competitive reaction for protein-binding in the presence of glutathione was again demonstrated. Sulphydryl compounds such as cysteine, ergothionine, homocysteine and thiolhistidine had little or no effect in either of the two systems, and the reaction therefore appears to be specific for glutathione. Oxidized glutathione was ineffective in increasing the yield of water-soluble metabolites indicating that the sulphydryl group was involved, and N-ethylmaleimide was found to be strongly inhibitory. The effect of estrogen oxidation products on the in vitro inactivation of gonadotropins was also investigated. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

Examination of Vicia amen'cana and Astragalus miser var. serotinus for estrogenic and anti-estrogenic activity demonstrated low potency uterotrophic compounds interfering with synthetic hormones in mammalian reproductive tracts. The potency of the extracts was affected by stage of growth. A toxic fraction was present in Astragalus miser var. serotinus at full bloom stage. Hormonal activity was not correlated with proximate analysis results for both species. Examination of the extract components revealed the overall structures of phenolic and aromatic compounds, including isoflavones, in a dynamic state throughout the growing season. The effects of topical fertilizer application on alsike clover (Trifolium hybridum), ladino clover (Trifolium repens var. ladino) and alfalfa (Medicago sativa) indicated that dry matter yields were slightly but insignificantly affected by fertilizer application. A method for the quantitative analysis of the free estrogenic isoflavones biochanin A and genistein was developed. Estimation of these two isoflavones, in addition to coumestrol and formononetin, illustrated that N, P and K applications would significantly affect the level of these plant sterols in the legume species. Alsike clover increased in total isoflavone content with phosphate addition; ladino clover increased total isoflavones to phosphate deficiency and complete fertilizers; alfalfa did not respond to fertilizer treatment. Total estrogenic compounds on a dry matter basis were less affected in the three species than were individual isoflavone components. / Land and Food Systems, Faculty of / Graduate