LD2668 .T4 1954 E9 / Master of Science

No description available.

Because of the structural resemblance to the female hormone, phytoestrogen is another important class of endocrine disruptor. In the present project, we evaluated the effects of phytoestrogens isoliquiritigenin (ILN), hesperetin (HES), genistein, (GEN) and naringenin (NAR) on estrogen metabolism and also their effects on MCF-7 tumor growth in ovariectomized nude mice. We found that these phytoestrogens had differential effect on MCF-7 xenografts. NAR and GEN had totally different responses in the tumor growth. In contrast, ILN and HES only deterred MCF-7 xenograft growth when CYP19 was overexpressed in the graft. / Breast cancer is one of the most prevalent female cancers in Hong Kong and western countries. Prolonged exposure to estrogen has been associated with increased risk of breast cancer. Many enzymes are responsible for estrogen metabolism, for instance, aromatase (CYP19) is responsible for biosynthesis; CYP1 family enzymes hydroxylate estrogen; COMT (catechol-O-methyltransferase) inactivates the hydroxyestrogen; and UDP-glucuronosyltransferase 1A1 (UGT1A1) eliminates the estrogen metabolites. In this project, we employed cell and animal models to address estrogen metabolism-related questions under the influence of endocrine disruptors. / TCDD is a prototype compound of a whole class of halogenated aromatic hydrocarbons termed dioxin-like contaminants, which are also known to be endocrine disruptors. Because of their persistence in the environment dioxins are one of the most concerned classes of carcinogens. Humans can be exposed to this pollutant through contaminated food, air, drinking water, etc. We found that pre-ovariectomy administration of TCDD could significantly reduce aromatase expression in the brain but increase the expression in the adipose tissue. Our results suggested that the timing of exposure to the toxicant could determine the estrogenicity of TCDD. / The present project indicated that endocrine disruptors can alter the metabolism of estrogen; however, the significance of this alteration may be specific to tissues' phenotype and the timing of exposure. / Ye Lan. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 169-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Alfalfa accumulates phytoestrogens and when ingested binds the estrogen receptor and induces morphological changes similar to endogenous estrogens. The objective of this study is to evaluate morphological changes in uteri, vulva, and teats of ovariectomized prepubertal ewe lambs. Eighteen prepubertal ewe lambs were ovariectomized in November 2000 and fed nonestrogenic hay until May 2001. In May, ewes were fed bentgrass straw and cottonseed meal. On day 0 of a 12-day feed trial, ewes were assigned randomly to three treatments (n=6 in each treatment): Estradiol, Control, and Alfalfa. Estradiol treated ewes were fed bentgrass straw and cottonseed meal ad libitum, plus receiving a daily injection of 10 mg estradiol-17�� suspended in corn oil. Control ewes were fed bentgrass straw and cottonseed meal ad libitum and received a daily injection of corn oil vehicle. Alfalfa ewes were fed alfalfa ad libitum and received a daily injection of corn oil vehicle. Three blinded observers assigned each ewe a subjective score ranging from 1 (no change) to 4 (significant change) for vulva and teat morphology on Days 0, 1, 3, 5, 7, 9 and 12. Teat length and circumference were measured on Days 1, 7 and 12. Ewes were slaughtered on Day 13, uteri were weighed, and a cross-section was collected from each uterine horn. Cross-sections were fixed in Lillie's Neutral Buffered Formalin and embedded in paraffin wax, sectioned at 4-5 ��m, and stained with hematoxylin and eosin. An ocular micrometer was used to measure luminal epithelial cell height. Estradiol treated ewes had heavier (p<0.05) uterine weights and greater (p<0.05) uterine luminal epithelial cell height than that of ewes fed alfalfa or control ewes. Uterine weights and uterine luminal epithelial cell height were greater (p<0.05) in alfalfa fed ewes than control ewes. Vulva scores for estradiol treated ewes were higher than those of control ewes (p<0.05). Alfalfa fed ewes had numerically higher vulva scores than control ewes but the difference was not significant statistically (p>0.05). Teat scores or measurements showed no differences (p>0.05) among treatments. Ewes exhibited slight changes in vulva scores due to treatment, but the most noted effects were observed in uterine growth. This research suggests that uterine weight and uterine luminal epithelial cell height are sensitive to the estrogenic activity of alfalfa and estradiol-17 resulting in morphological changes in estrogen target tissues in the prepubertal ewe lamb. / Graduation date: 2003

Graduation date: 1996

The morphologic effects of estrogen withdrawal from an estrogen-dependent tumor were investigated using light and electron microscopy. Twenty-five male hooded rats received interscapular implants of an estrogen-induced, estrogen-dependent adrenocortical tumor as well as subcutaneous estrone pellets. The tumors were examined when they had reached one and two centimeters in size. The pellets were removed from a second group and the tumors examined when they had decreased to a minimum size. A third group received a second pellet after the tumor had regressed to a minimum size following removal of the first pellet. The primary tumors were characterized by plump, active-looking cells growing usually in a sheet-like pattern. The ultrastructural features of these tumors included large, bizarre mitochondria with tubular cristae, prominent polyribosomal aggregates and Golgi zones as well as fairly frequent centrioles. The regressing tumors consisted of smaller cells growing in a trabecular pattern and heavily infiltrated with eosinophils. The fine structure of the tumor cells consisted of small mitochondria with a dense matrix and a few irregular cristae. Myelin figures and residual bodies were present in significant numbers only in the regressing tumors while (primary)lysosomes were more frequent in the growing tumors. The tumors examined after reimplantation of estrone showed features of the primary growth tumors plus residual foci of regression. It thus appears that estrogen acts as a trophic factor for this experimental tumor much as it does for the uterus. Tumor cells can survive in its absence, but require it for growth. The ultrastructural expression of estrogen administration seen in this study is the proliferation of mitochondria as an energy source and polyribosomes for the production of proteins for endogenous consumption. The removal of estrogen results in a generalized reduction in cellular activity and an accumulation of the products of autophagy. Further work is required to tie in these results with the studies being done on the basic mechanisms of estrogen action at the level of molecular biology. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Thesis (MSc)--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: The aim of this study was to build a mathematical model that describes the binding of 17- -estradiol (E2) to estrogen receptor (ER- ) and the influence the sex hormone binding globulin (SHBG) has on this interaction. The influence of SHBG on the transactivation of an estrogen response element, via ligand bound ER- , was also studied. COS-1 cells, derived from the kidney of a green african monkey, were used to study the binding of E2 to ER- in the absence of SHBG. The influence of SHBG on the binding of E2 to ER- was studied using Hep89 cells, human hepatacoma carcinoma, which express SHBG endogenously and are stably transfected with the ER- gene. Human pregnancy plasma was used to study the interaction of E2 with SHBG in the absence of ER- . The results of this study have shown that the Kd (E2) for ER- was determined as between 3.4nM and 4.4nM in the absence of SHBG. With respect to the binding of E2 to ER- it was not possible to determine the Kd app and Bmax for ER- using the Hep89 experimental system. The Kd (E2) for SHBG was not determined using the human pregnancy plasma experimental system. With the aid of mathematical modelling, a model of the Hep89 and human pregnancy plasma experimental systems, was built. The results of the numerical modelling, using mathematical modelling, showed that the presence of albumin together with SHBG was the reason that the Kd app (E2) could not be determined in the Hep89 experimental system. With respect to the use of human pregnancy plasma to determine the Kd (E2) for SHBG it was shown that if the plasma was diluted 200 times it would have been possible to determine the Kd app (E2) for SHBG, in the presence of albumin. Ligand independent transactivation of an estrogen response element was shown to be a problem in the COS-1 cell system when promoter reporter gene assays were undertaken. As COS-1 cells were used as a control for the absence of SHBG no further promoter reporter gene assays were undertaken using the Hep89 experimental system. / AFRIKAANSE OPSOMMING: Die doel van hierdie studie was die bou van ‘n wiskundige model wat die verbinding van E2 met die estrogeenreseptor (ER- ) en die invloed wat die geslagshormoon-verbindingglobulien (SHBG) op hierdie interaksie het, beskryf. Die effek van SHBG op die transaktivering van ‘n estrogeen responselement, via die ligandverbonde ER- , is ook bestudeer. COS-1-selle uit die nier van ‘n groen afrika-aap is gebruik om die verbinding van E2 met ER- in die afwesigheid van SHBG te bestudeer. Die invloed van SHBG op die verbinding van E2 met ER- , is bestudeer deur gebruik te maak van Hep89-selle, die menslike lewergeswelkarsinoom, wat SHBG uitwendig afgee en wat stabiel getransfesteer kan word met die ER- geen. Menslike swangerskapplasma is gebruik om die interaksie van E2 met SHBG in die afwesigheid van ER- te bestudeer. Die uitslag van hierdie studie toon aan dat die Kd (E2) vir ER- vasgestel tussen 3.4nM en 4.4nM in die afwesigheid van SHBG. Met betrekking tot die verbinding van E2 met ER- , was dit nie moontlik om die Kd (E2) en Bmax app vir ER- met die gebruik van die Hep89 eksperimentele stelsel vas te stel nie. Die Kd (E2) vir SHBG is nie vasgestel deur die gebruik van die menslike swangerskapplasma eksperimentele stelsel nie. ‘n Model van die Hep89 en menslike swangerskapplasma eksperimentele stelsels is met behulp van wiskundige modellering gebou. Die uitslag van die numeriese modellering, met gebruik van wiskundige modellering, toon dat die teenwoordigheid van albumien, saam met SHBG, die rede was dat die Kd app (E2) nie in die Hep89 eksperimentele stelsel vasgestel kon word nie. Wat betref die gebruik van menslike swangerskapplasma om die Kd (E2) vir SHBG vas te stel, is daar aangetoon dat, indien die plasma 200 maal verdun was, dit moontlik sou gewees het om die Kd app (E2) vir SHBG in die teenwoordigheid van albumien vas te stel. Promotor verkilkkergeen toetse het ligandonafhanklike transaktiveering van ‘n estrogeen responselement aangetoon as ‘n probleem in die COS-1-selle stelsel. Omdat COS-1-selle gebruik is as ‘n kontrole vir die afwesigheid van SHBG, is geen verdere promotor verkilkkergeen toetse onderneem met die gebruik van die Hep89 eksperimentele stelsel nie.

Dong, Jinghui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 106-130). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Lee Chung-hung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 113-133). / Abstracts in English and Chinese. / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- History of soybean --- p.1 / Chapter 1.2 --- Health benefits of soybean --- p.2 / Chapter 1.3 --- Introduction to flavonoids --- p.3 / Chapter 1.4 --- Bioavailability of flavonoids --- p.5 / Chapter 1.5 --- Chemistry of isoflavones --- p.6 / Chapter 1.6 --- Estrogenic property of isoflavones --- p.8 / Chapter 1.7 --- Nutritional significance of isoflavones and their glycosides --- p.8 / Chapter 1.7.1 --- Anticarcinogenic activity --- p.9 / Chapter 1.7.2 --- Antioxidative activity --- p.10 / Chapter 1.7.3 --- Cardioprotective activity --- p.13 / Chapter 1.7.4 --- Osteoprotective activity --- p.14 / Chapter 1.7.5 --- Neuroprotective activity --- p.15 / Chapter 1.7.6 --- Antiangiogenic activity --- p.16 / Chapter Chapter 2 --- Composition of Soybean Isoflavones / Chapter 2.1 --- Introduction --- p.17 / Chapter 2.2 --- Objective --- p.19 / Chapter 2.3 --- Materials and Methods --- p.20 / Chapter 2.3.1 --- Extraction and isolation --- p.20 / Chapter 2.3.1.1 --- Preparation of soybean butanol extract --- p.20 / Chapter 2.3.1.2 --- Preparation of isoflavones and their glycosides from soybean butanol extract --- p.20 / Chapter 2.3.2 --- HPLC analysis --- p.21 / Chapter 2.3.2.1 --- Sample preparation for the HPLC analysis --- p.21 / Chapter 2.3.2.2 --- HPLC analysis --- p.22 / Chapter 2.3.2.3 --- Quantification of the flavonoids and their glycosides --- p.24 / Chapter 2.4 --- Results --- p.25 / Chapter 2.4.1 --- Structural identification --- p.25 / Chapter 2.4.1.1 --- Compound 1 --- p.25 / Chapter 2.4.1.2 --- Compound 2 --- p.26 / Chapter 2.4.1.3 --- Compound 3 --- p.26 / Chapter 2.4.1.4 --- Compound 4 --- p.27 / Chapter 2.4.1.5 --- Compound 5 --- p.27 / Chapter 2.4.1.6 --- Compound 6 --- p.28 / Chapter 2.4.1.7 --- Compound 7 --- p.28 / Chapter 2.4.1.8 --- Compound 8 --- p.29 / Chapter 2.4.2 --- Quantification of isoflavones in traditional Chinese foods --- p.29 / Chapter 2.5 --- Discussion --- p.32 / Chapter Chapter 3 --- Hypocholesterolemic Effects of Soymilkin Hamsters / Chapter 3.1 --- Introduction --- p.35 / Chapter 3.1.1 --- Lipoproteins and their functions --- p.35 / Chapter 3.1.2 --- Risk factors of cardiovascular disease --- p.36 / Chapter 3.1.3 --- Hamster as an animal model of cholesterol metabolism --- p.38 / Chapter 3.2 --- Objective --- p.39 / Chapter 3.3 --- Materials and Methods --- p.40 / Chapter 3.3.1 --- Preparation of soymilk --- p.40 / Chapter 3.3.2 --- Animals --- p.40 / Chapter 3.3.2.1 --- Experiment one - Hypocholesterolemic effect of soymilk in hamsters --- p.40 / Chapter 3.3.2.1 --- Experiment two 一 The effect of fluid cross-over between soymilk and cow´ة s milk on serum cholesterol in hamsters --- p.41 / Chapter 3.3.3 --- Serum lipid and lipoprotein determinations --- p.42 / Chapter 3.3.4 --- Determination of cholesterol in organs --- p.42 / Chapter 3.3.5 --- Statistics --- p.43 / Chapter 3.4 --- Results --- p.46 / Chapter 3.4.1 --- Experiment one-Hypocholesterolemic effect of soymilk in hamsters --- p.46 / Chapter 3.4.1.1 --- Growth and food intake --- p.46 / Chapter 3.4.1.2 --- "Effect of SM and CM on TG, TC and HDL-C" --- p.46 / Chapter 3.4.1.3 --- Effect of SM and CM on non-HDL-C and ratio of non-HDL-C to HDL-C --- p.46 / Chapter 3.4.1.4 --- Effect of SM and CM on concentration of hepatic cholesterol --- p.47 / Chapter 3.4.1.5 --- "Effect of SM and CM on brain, heart and kidney cholesterol" --- p.47 / Chapter 3.4.2 --- Experiment two - The effect of fluid cross-over between soymilk and cow´ةs milk on serum cholesterol in hamsters --- p.52 / Chapter 3.4.2.1 --- Growth and food intake --- p.52 / Chapter 3.4.2.2 --- Effect of fluid cross-over on serum TC --- p.52 / Chapter 3.5 --- Discussion --- p.55 / Chapter Chapter 4 --- Antioxidant Activities of Soybean Isoflavones and Their Glycosides / Chapter 4.1 --- Introduction --- p.58 / Chapter 4.1.1 --- Role of low density lipoprotein oxidation in the development of atherosclerosis --- p.59 / Chapter 4.1.2 --- LDL oxidation --- p.61 / Chapter 4.1.3 --- Thiobarbituric acid reactive substances (TBARS) as an index of LDL oxidation --- p.62 / Chapter 4.1.4 --- "The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power""" --- p.65 / Chapter 4.1.5 --- "1,1-diphenyl-2-picrylhydrazyl (DPPH) as a measure of free radical scavenging capacity" --- p.65 / Chapter 4.1.6 --- Antioxidant and LDL oxidation --- p.65 / Chapter 4.2 --- Objective --- p.67 / Chapter 4.3 --- Materials and Methods --- p.68 / Chapter 4.3.1 --- Preparation of samples --- p.68 / Chapter 4.3.2 --- Isolation of LDL from human serum --- p.68 / Chapter 4.3.3 --- LDL oxidation --- p.69 / Chapter 4.3.4 --- TBARS assay --- p.69 / Chapter 4.3.5 --- FRAP assay --- p.70 / Chapter 4.3.6 --- DPPH assay --- p.71 / Chapter 4.3.7 --- Statistics --- p.72 / Chapter 4.4 --- Results --- p.73 / Chapter 4.4.1 --- Effects of seven individual soybean isoflavones and their glycosides on LDL oxidation --- p.73 / Chapter 4.4.2 --- The antioxidant power of individual soybean isoflavones and their glycosides in the FRAP assay --- p.73 / Chapter 4.4.3 --- Activity of individual soybean isoflavones and their glycosides as radical scavenging antioxidants --- p.74 / Chapter 4.5 --- Discussion --- p.78 / Chapter Chapter 5 --- Hypocholesterolemic Effects of Soybean Isoflavones in Ovariectomized Golden Syrian Hamsters / Chapter 5.1 --- Introduction --- p.83 / Chapter 5.1.1 --- Coronary heart disease in women --- p.83 / Chapter 5.1.2 --- Menopause as a risk factor in CHD --- p.84 / Chapter 5.1.3 --- Dietary soy in treating postmenopausal hypercholesterolemia --- p.85 / Chapter 5.2 --- Objective --- p.87 / Chapter 5.3 --- Materials and Methods --- p.88 / Chapter 5.3.1 --- Preparation of soymilk --- p.88 / Chapter 5.3.2 --- Preparation of soybean extract --- p.88 / Chapter 5.3.3 --- Animals --- p.89 / Chapter 5.3.4 --- Serum lipid determinations --- p.90 / Chapter 5.3.5 --- Determination of tissue cholesterol content --- p.90 / Chapter 5.3.6 --- Extraction of neutral and acidic sterols from fecal samples --- p.90 / Chapter 5.3.6.1 --- Determination of neutral sterols --- p.91 / Chapter 5.3.6.2 --- Determination of acidic sterols --- p.92 / Chapter 5.3.6.3 --- GLC analysis of neutral and acidic sterols --- p.92 / Chapter 5.3.7 --- Statistics --- p.93 / Chapter 5.4 --- Results --- p.96 / Chapter 5.4.1 --- Growth and food intake --- p.96 / Chapter 5.4.2 --- Effect of ovariectomy on serum TC --- p.96 / Chapter 5.4.3 --- "Effect of soymilk and soybean extract on serum TC,TG and HDL-C" --- p.96 / Chapter 5.4.4 --- Effect of soymilk and soybean extract on non-HDL-C and ratio of non- HDL-C to HDL-C --- p.97 / Chapter 5.4.5 --- Effect of soymilk and soybean extract on concentration of hepatic cholesterol --- p.97 / Chapter 5.4.6 --- Effect of soymilk and soybean extract on heart and kidney cholesterol --- p.97 / Chapter 5.4.7 --- Effect of soymilk and soybean extract on fecal neutral and acidic sterols --- p.103 / Chapter 5.5 --- Discussion --- p.106 / Chapter Chapter 6 --- Conclusion --- p.110 / References --- p.113

Abstract not available