Dissertations / Theses on the topic 'Phytoestrogens'
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1
Leu, Chao-Wei Chemistry Faculty of Science UNSW. "Synthesis of heterocyclic analogues of phytoestrogens." Publisher:University of New South Wales. Chemistry, 2008. http://handle.unsw.edu.au/1959.4/40824.
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The pyrrolo[3,2,1-ij]quinolin-6-one ring system was synthesised from 3-aryl-4,6-dimethoxyindoles and 2,3-disubstituted-4,6-dimethoxyindoles. The reaction of 4,6-dimethoxyindoles under Friedel-Crafts or Vilsmeier-Haack acylation gave the 2- and 7-indolyldeoxybenzoins in good yield. Cyclisation of 7-indolyldeoxybenzoins with N,N-dimethylformamide dimethyl acetal as a one carbon reagent gave the pyrroloquinolin-6-ones in high yield. Reduction of pyrroloquinolin-6-ones with hydrogen gas and 10% palladium on carbon or lithium aluminium hydride yielded the dihydropyrroloquinolin-6-ones. Demethylation of pyrroloquinolin-6-ones with 48% hydrobromic acid in glacial acetic acid gave a mixture of the monohydroxy and dihydroxy analogues in high yield. The synthesis of quinolin-4-ones using the Conrad-Limpach method was attempted using three different cyclisation conditions such as Dowtherm A, polyphosphoric acid and a mixture of diphenyl ether and methanesulfonic acid. Quinolin-2-ones such as 4-methyl-3-aryl-, 3,4-diaryl- and 3-aryl-4-benzyl-5,7-dimethoxyquinolin-2-ones could be synthesised from either the N-phenylacetylaniline or the N-trifluoroacetyl aniline strategy. Attempted reduction of the quinolin-2-ones with standard metal hydride reagents was unsuccessful. However reduction was achieved via the conversion of quinolin-2-one to the corresponding 2-chloroquinoline followed by reaction of the chloroquinoline with zinc powder and glacial acetic acid to produce a novel, highly substituted quinoline system. Demethylation was successfully carried out with 48% hydrobromic acid in glacial acetic acid to give the trihydroxyquinolin-2-one in high yield. The reactions of 4-substituted-5,7-dimethoxyquinolin-2-ones and the corresponding 2-chloroquinolines as potential organic intermediates were explored. Facile formylation of both quinolin-2-ones and 2-chloroquinolines was observed under Vilsmeier-Haack conditions while acetylation was successful under Friedel-Crafts conditions using antimony (V) pentachloride as the Lewis acid. Further reaction of 8-formyl-quinolin-2-one with 1,2-diaminobenzene in N,N-dimethylformamide led to the formation of a new 8-(benzimidazolyl)-quinolin-2-one ring system. The quinolin-2-ones exhibited selective electrophilic substitution at the C8 position for a range of reactions. However, an unexpected nitration occurred at the C3 position for the 4-methoxy and 4-phenyl-5,7-dimethoxyquinolin-2-ones with good yields. A series of novel 4,6-hydroxylindoles was successfully synthesised from the corresponding methoxy analogues in high yield using anhydrous aluminium chloride. When 3-(4-bromophenyl)-4,6-dimethoxyindole was reacted with 48% hydrobromic acid in glacial acetic acid a 2,2?-indolylindoline dimer was formed. The 5,7-dihydroxyquinolin-2-ones were similarly synthesised in high yield using anhydrous aluminium chloride in chlorobenzene.
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Lanceman, Dorothy Melinda. "Do phytoestrogens disrupt endogenous oestrogen metabolism?" Thesis, University of Birmingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410279.
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Dinauer, Christina Marie. "Analysis of in vitro binding of dietary fibers by the phytoestrogen, daidzein, in the presence and absence of iron." Online version, 2000. http://www.uwstout.edu/lib/thesis/2000/2000dinauerc.pdf.
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Glover, Amy, and n/a. "The effect of dietary phytoestrogens on male fertility." University of Otago. Department of Anatomy & Structural Biology, 2006. http://adt.otago.ac.nz./public/adt-NZDU20070711.140602.
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Phytoestrogens are plant-derived compounds with oestrogenic activity. They are common in both human and animal diets, particularly through soy-based foods. This study assessed whether the reproductive function of male rats is affected by exposure to a high phytoestrogen diet during adulthood and examined possible mechanisms through which phytoestrogens may disrupt reproductive function. Experiments focused on the epididymis, a steroid-regulated organ responsible for the maturation, transport, and storage of sperm.
Adult male rats, bred and raised on a low phytoestrogen diet, were either transferred to a high phytoestrogen diet (experimental), or remained on the low phytoestrogen diet (control). Litter size is a measure of fecundity and after 3 days on the high phytoestrogen diet litter size was reduced. This effect on fecundity was transient as litter sizes returned to control levels by day 12. The reduced fecundity at day 3 could not be explained by changes in sperm concentration. Plasma gonadotrophin levels and testicular testosterone levels were not affected by phytoestrogen exposure, however, the expression of steroid hormone receptors in the epididymis was affected, coincidental with reduced fecundity. The gene expression of oestrogen receptor alpha and androgen receptor was increased in the initial segment of the epididymis and decreased in the cauda epididymis. Additionally, lipid peroxidation of epididymal sperm was significantly increased in rats fed the high phytoestrogen diet for 3 days.
It is concluded that acute exposure to the high phytoestrogen diet disrupts the steroid regulation of the epididymis, disrupting its normal function. This results in decreased sperm quality, thereby reducing fecundity.
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Mfenyana, Ciko. "Selective extraction of Cyclopia for enhanced in vitro phytoestrogenicity /." Link to the online version, 2008. http://hdl.handle.net/10019/783.
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Bakshi, Vibhu Smith Don Wiley. "In vitro cultures of Morus alba for enhancing production of phytoestrogens." [Denton, Tex.] : University of North Texas, 2009. http://digital.library.unt.edu/ark:/67531/metadc12078.
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Bylund, Annika. "Phytoestrogens and prostate cancer : experimental, clinical, and epidemiological studies." Doctoral thesis, Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1402.
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Ogegbo, Olumuyiwa Lateefah. "Quantitative analysis and metabonomic study of phytoestrogens in Africans." Thesis, London Metropolitan University, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507096.
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West, M. "Effects of dietary phytoestrogens on spermatogenesis and sperm function." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426916.
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Pfeiffer, Thomas J. "Phytoestrogens may inhibit proliferation of MCF-7 cells, an estrogen-responsive breast adenocarcinoma cell line." Link to electronic thesis, 2004. http://www.wpi.edu/Pubs/ETD/Available/etd-0430104-132238.
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Chan, Yap-hang, and 陳熠恆. "Role of phytoestrogen in vascular function and dysfunction." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40733725.
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Chan, Yap-hang. "Role of phytoestrogen in vascular function and dysfunction." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40733725.
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Pratt, Latanya R. "The effects of Phytoestrogens on Estrogen α and β receptor expression in the brain of the male Syrian Hamster." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2007. http://digitalcommons.auctr.edu/dissertations/14.
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Phytoestrogens are diphenolic, non steroidal compounds which are present in plants and are consumed by both humans and animals. Previous investigations have demonstrated that dietary phytoestrogens appear to have neurobehavioral effects on intermale aggression in male Syrian hamsters and the neural mechanisms require further exploration. In this study experiments involving a phytoestrogen (PE) and a phytoestrogen free (PE Free) diet were performed to determine whether or not diet had an effect on the expression of a and p estrogen receptors in the brain of male Syrian hamsters (Mesocricetus auratus). Twenty male hamsters were used for experimentation and animals were divided into a PE (n = 10) and a PE Free group (n = 10) for a period of 3 weeks. Animals were sacrificed, perfused and brains removed for subsequent protein extraction and immunohistochemisty. Estrogen receptors were quantified using western blot utilizing brains from both the PE and the PE Free group. Results revealed a wide spread distribution of estrogen receptors throughout the brain of male Syrian hamsters. Positive irnmunoreactive labeling was observed in the thalamus, hypothalamus, amygdala, cortex and hipoocampus. Sections were matched and comparisons were made to determine which estrogen receptor had a higher rate of expression. Results revealed higher levels of ERP binding in comparison to ERa. In addition, there appeared to be a higher expression of estrogen receptors in animals on the PE Free diet (p < 0.05). Overall, results obtained form western blots support the hypothesis that animals on the PE Free diet experienced an increase in ER expression. Moreover, immunohistochemistry revealed visual differences of estrogen receptor expression in the brain and data suggests that a diet lacking phytoestrogens can up regulate estrogen receptors in male hamsters. In summary, we have demonstrated that manipulating the diet can have neurobiological consequences and future research should consider diet as a significant factor in experimental research on the brain.
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Larkin, Theresa Anne. "Soy isoflavone bioavailability effects of probiotic and prebiotic consumption and oil supplementation /." Access electronically, 2005. http://www.library.uow.edu.au/adt-NWU/public/adt-NWU20060123.133532/index.html.
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Bakshi, Vibhu. "In vitro Cultures of Morus alba for Enhancing Production of Phytoestrogens." Thesis, University of North Texas, 2009. https://digital.library.unt.edu/ark:/67531/metadc12078/.
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Plant estrogens have long been associated with health benefits. The potential of tissue culture techniques for the production of several secondary metabolites has been known for many years. Tissue cultures stimulate the production or induce the biosynthesis of novel compounds not found in the mature plant. Tissue culture of Morus alba, family Moraceae, is known to contain phytoestrogens, was established on plant-hormone supplemented Murashige and Skoog (MS) medium. Petiole and the stem tissue from mature trees were the best explants for initiation and proliferation of calli. The best callus proliferation was obtained on MS medium containing 1-napthalene acetic acid (1mg/ml) and benzylaminopurine (0.5mg/ml) for M. alba. Comparison of phytoestrogens of Moraceae species from in vivo and in vitro tissue isolation were carried out. The estrogenic activities of callus extracts were assayed in an estrogen-responsive yeast system expressing the human estrogen receptor alpha. Male callus extracts had higher estrogenic activity than male and female extracts from in vivo and in vitro tissues. Isolation and characterization of phytoestrogens from above tissues were carried out using solid phase extraction, high perfomance liquid chromatography and mass spectrometry techniques. Biochanin A, an isoflavonoid, was isolated as one of the compounds in male callus extracts. Biochanin A has been known to have an antiestrogenic acitivity in mammals. Isoflavonoid compounds have been characterized as strong protein tyrosine kinase inhibitors in variety of animal cells. Isoflavones are structurally similar to estradiol, and display agonistic and antagonistic interactions with the estrogen receptor. Isoflavones possess therapeutic and preventive properties such as being used for postmenopausal osteoporosis, breast cancer, and inhibition of tumors.
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Meliala, Andreanyta 1971. "Dietary phytoestrogens and hormone-related health conditions in men and women." Monash University, Monash Asia Institute, 2002. http://arrow.monash.edu.au/hdl/1959.1/8504.
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Li, Wei. "Exploration of the underlying mechanisms for the superinduction effects of phytoestrogens /." Available to subscribers only, 2006. http://proquest.umi.com/pqdweb?did=1208135141&sid=7&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Green, Christopher C. "Effects of phytoestrogens on sensitive life history stages in channel catfish /." Available to subscribers only, 2007. http://proquest.umi.com/pqdweb?did=1456624541&sid=12&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Hertrampf, Torsten. "Analyse molekularer Mechanismen der ERα- und ERβ-vermittelten Wirkung spezifischer Liganden und des Phytoestrogens Genistein." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2007. http://nbn-resolving.de/urn:nbn:de:swb:14-1180003908058-30532.
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Die Behandlung menopausaler und postmenopausaler Beschwerden ist mit einem erhöhten Risiko verbunden, an Mamma- und Endometriumskarzinomen zu erkranken. Darüber hinaus zeigen epidemiologische Studien, dass in ostasiatischen Ländern postmenopausale Beschwerden, osteoporotische Frakturen und Herz-Kreislauferkrankungen seltener auftreten als in westlichen Ländern. Vor diesem Hintergrund war es Ziel der Untersuchungen dieser Arbeit, in dem Tiermodell der ovarektomierten Ratte die mögliche Bedeutung von estrogenrezeptorsubtypspezifischen Einflüssen für hormonell bedingte Erkrankungen und Beschwerden zu untersuchen. Hierbei sollten gewebespezifische Wirkungen estrogenrezeptorsubtypspezifischer Liganden untersucht und explizit die Bedeutung der Estrogenrezeptorsubtypen ERα und ERβ bei der Gewebehomöostase in Knochen und Darm analysiert werden. Darüber hinaus sollten vor dem Hintergrund estrogenrezeptorsubtypspezifischer Wirkungsweisen gewebespezifische Einflüsse des Phytoestrogens Genistein (Gen) näher charakterisiert werden. Es konnte gezeigt werden, dass nach einer subkutanen Applikation der knochenprotektive Einfluss von Gen mit dem von Estradiol (E2) vergleichbar ist, durch die Kombination mit Bewegung verstärkt wird und über den ERα vermittelt zu sein scheint. Es zeigte sich außerdem, dass der stimulierende Einfluss von E2 auf den motorischen Antrieb ERα-vermittelt ist und ERβ-spezifische Liganden ebenso wie Gen diesen Effekt antagonisieren. Des Weiteren wurde deutlich, dass E2, nicht aber Gen über den ERα Einfluss auf die Körperfettverteilung nimmt. Mit einer phytoestrogenreichen Diät konnten in adulten Ratten physiologisch relevante Gen/Dai-Plasmaspiegel erreicht werden, allerdings blieben hierbei die nach einer subkutanen Applikation beobachteten knochenprotektiven Effekte dieser Phytoestrogene aus. Bei der näheren Betrachtung der Gewebehomöostase im Dünndarm zeigte sich, dass über den im Darm verstärkt exprimierten ERβ antiproliferative und proapoptotische Effekte vermittelt werden und Gen in diesem Gewebe wie ein ERβ-spezifischer Agonist wirkt. Bezogen auf eine hormonell bedingte Osteoporose, wie sie bei einem Großteil postmenopausaler Frauen auftritt, scheint das Phytoestrogen Genistein eine mögliche Alternative zur Hormonersatztherapie darzustellen. Außerdem zeigt sich, dass Genistein gewebe- und estrogenrezeptorsubtypspezifische antagonistische und agonistische Einflüsse hat und somit die Charakterisierung als „Phyto-SERMs“ (pflanzlicher selektiver Estrogenrezeptormodulator) zutreffend ist. Sollten sich in weiterführenden Studien die beobachteten Effekte im Dünndarm auch für die Gewebehomöostase im Kolon beschreiben lassen, können vor diesem Hintergrund Genistein und ERβ-spezifische Liganden für die Darmkrebsprävention diskutiert werden…
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Pearce, Virginia. "A Novel Phytoestrogen that Acts as an Agonist for Human Estrogen Receptors." Thesis, University of North Texas, 2001. https://digital.library.unt.edu/ark:/67531/metadc3003/.
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Estrogen is the natural agonist of the estrogen receptor (ER). However, certain plant-derived compounds or phytoestrogens have been identified that mimic estrogens and act as agonists and/or antagonists of ERs, depending on subtype and target tissue. Understanding how phytoestrogens interact with ERs, and therefore effect the estrogenic response, may prove beneficial in hormone replacement therapy and in the prevention and treatment of hormone-related diseases. Using Thin Layer Chromatography, gas chromatography/mass spectrometry (GC/MS), and proton nuclear nagnetic resonance (HNMR), I identified 4-ethoxymethylphenol (4EM) found in Maclura pomifera. While most phytoestrogens are heterocyclic compounds, 4EM is a simple phenol that acts as an agonist of ER-alpha and -beta in HeLa and MCF-7 cells. To study the effect of 4EM on ER-alpha and -beta activity, I performed transient transfection assays and showed that 4EM activates ER dependent gene transcription in a dose dependent manner in both ER subtypes. Further, 4EM- mediated transcription in ER-alpha, like estrogen, was enhance in the presense of co-activators, SRC-1 (steroid receptor coactivator-1), CBP (CREB binding proteins), and E6-AP (E6-associated protein) and inhibited by trans-4- hydroxytamoxifen (4HT). I found that 4EM was specific for ER and did not activate transcription of the progesterone receptor in HeLa cells.
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Ngan, Mo-yin Michelle. "The effects of soy phytoestrogens and vitamin E on prostate cancer cells /." Available to subscribers only, 2006. http://proquest.umi.com/pqdweb?did=1240698691&sid=19&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Karieb, Sahar Saadi. "The effect of phytoestrogens on bone and T cells' differentiation and activity." Thesis, University of Plymouth, 2012. http://hdl.handle.net/10026.1/1237.
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The fall in circulating oestrogen (E2) after the menopause leads to an increased rate of bone remodelling, excessive osteoclast activity and a greater fracture risk. Until recently hormone replacement therapy (HRT) was prescribed to post-menopausal women to prevent bone loss, however HRT is associated with an elevated incidence of cardiovascular disease, stroke and cancer. These side-effects led to an interest in naturally occurring compounds with oestrogenic action such as phytoestrogens (PEs), which are non-steroidal-plant derived compounds. Human trials and animal studies suggest a beneficial effect of PEs on bone mass, although their ability to modify osteoclast formation in response to key inflammatory cytokines has not been examined. The aim of the following studies was to determine the effect of physiologically relevant concentrations of genistein, coumestrol and daidzein on TNF-α-induced osteoclast formation, osteoblasts differentiation and T cell activity. Genistein (10-7 M), daidzein (10-5 M), and coumestrol (10-7 M) significantly reduced TNF-α-induced TRAP positive osteoclast formation and bone resorption, which was prevented by the E2 antagonist ICI 182,780. The suppressive action on osteoclast formation was associated with a significant reduction in TNF-α-induced c-fos and NFATc1 mRNA expression and NFATc1 nuclear translocation. Constitutive c-fos expression prevented the inhibitory action of PEs on osteoclast differentiation, resorption and NFATc1 expression. The effect of PEs, in the presence or absence of the anabolic nutritional factor zinc, on osteoblasts differentiation and bone nodule formation was examined in-vitro. Coumestrol (10-5 to 10-7 M), daidzein (10-5 to 10-6 M) and genistein (10-5 M) enhanced bone nodule formation and ALP activity in human osteoblasts, and this effect was significantly augmented in the presence of zinc (10-5 M). Furthermore, PEs and zinc increased Runx2 mRNA expression and Zn2+ augmented the inhibitory effect of PEs on RANKL/OPG ratio. This suggests that in addition to the direct inhibitory effect on osteoclast formation PEs also in-directly reduce the osteoblastsic stimulus for osteoclast formation and promote bone formation. E2 deficiency is thought to promote osteoclastogenesis by modifying Thelper1 (Th1) cell proliferation and inflammatory cytokine production in particular TNF-α. I therefore examined the effect of PEs on T cell proliferation and inflammatory cytokine production. All PEs prevented the augmentative effect of con A stimulated T cells on osteoclast formation in co-culture. However the mechanism of action varied, genistein reduced con A stimulated TNF-α, IL-1β and RANKL expression with little effect on viability, coumestrol decreased cell viability and TNF-α expression whereas the inhibitory effect of daidzein was mediated via suppression of viable T cell number. This study provides novel evidence that PEs have multiple effects on bone cell activity, directly inhibiting TNF-α-induced osteoclast formation, reducing the osteoblasts and T cell derived stimulus for osteoclast formation and augmenting osteoblasts differentiation and bone formation. Thus, PEs have a potential role in the treatment of post-menopausal osteoporosis and inflammatory skeletal disorders and that the beneficial effect noted in previous studies is mediated through multiple mechanisms.
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Low, Yen Ling. "Phytoestrogens : interactions with hormonal status and gene variants in a British population." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613663.
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Maier, Camelia G. A. (Camelia Gabriela-Anca). "Phytoestrogens in Two Dioecious Species: Isolation, Characterization and Role in Plant Reproduction." Thesis, University of North Texas, 1996. https://digital.library.unt.edu/ark:/67531/metadc332478/.
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A highly specific steroid regulated transcription system system in Saccharomyces cerevisae was used to screen for phytoestrogens indioecious plants. Yeast cells were co-transformed with a human estrogen receptor expression plasmid and a reporter plasmid containing the E. coli β-galactosidase gene.
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Mazur, Witold. "Phytoestrogens : occurrance in foods, and metabolism of lignans in man and pigs." Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/mazur/.
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Stevenson, Lindsay Marie. "Effects of soy phytoestrogen genistein on the reproductive development of immature female broiler chickens." Auburn, Ala., 2007. http://repo.lib.auburn.edu/2007%20Spring%20Theses/STEVENSON_LINDSAY_35.pdf.
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Day, John Kevin. "The use of ER[alpha]KO mouse models to study DNA methylation and the effects of genistein on tumor progression /." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3036820.
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Mahn, Katharina. "Acute and chronic effects of oestrogens and phytoestrogens on vascular reactivity in rats." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415012.
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McVey, Mark. "Mechanisms of effects of phytoestrogens on reproduction, steroidogenesis and steroid action in male rats." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26715.
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The consequences of soy isoflavone consumption on steroidogenesis were examined in F1 male rats from a multi-generation reproduction study investigating the effects of diets varying in isoflavone content. F1 male rats were obtained from a multi-generation study where the parental generation was fed diets containing alcohol-washed soy protein supplemented with increasing amounts of Novasoy, a commercially available isoflavone supplement. A control group was maintained on a soy-free casein-based diet (AIN93G). Testicular and serum androgen levels were assayed with commercial kits and were approximately doubled at postnatal day (PND) 120 for rats fed a diet of elevated levels of isoflavones. Steroidogenic enzyme activities were significantly increased at PND 28 and immunohistochemistry revealed approximately 25% greater numbers of Leydig cells stained for steroidogenic factor 1 at both PND 28 and 120 amongst rats fed elevated levels of isoflavones, resembling high human consumption rates. These findings show that F1 male rats continuously exposed to a mixture of dietary soy isoflavones from conception onwards exhibit altered gene expression at PND 28, which may lead to increased microsomal steroidogenic enzyme activity at this age and serum and testicular androgen profiles in adulthood. (Abstract shortened by UMI.)
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Owen, Alice. "The effects of estrogens and phytoestrogens on the metabolism and oxidation of plasma lipoproteins /." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09pho968.pdf.
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Pan, Meixia, and 潘妹霞. "Effects of phytoestrogens on hippocampal neuron proliferation and spatial memory performance in ovariectomized rats." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B4370377X.
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Gunnarsson, David. "Reproductive toxicology of endocrine disruptors : effects of cadmium, phthalates and phytoestrogens on testicular steroidogenesis." Doctoral thesis, Umeå : Department of Molecular Biology, Umeå University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1876.
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Pan, Meixia. "Effects of phytoestrogens on hippocampal neuron proliferation and spatial memory performance in ovariectomized rats." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B4370377X.
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Cardoso, Julio Roquete. "Efeitos da exposição a isoflavonas da soja sobre a saude reprodutiva de coelhos machos." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/318000.
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Orientador: Sonia Nair BaoTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Este estudo foi proposto para avaliar se a exposição perinatal (gestacional e lactacional) ou crônica a isoflavonas em dieta contendo soja ou na forma de concentrados de isoflavonas pode comprometer a saúde reprodutiva de coelhos machos. No primeiro experimento, fêmeas foram alimentadas com dieta contendo soja ou dieta isenta de soja e alfafa, suplementada com 10 ou 20 mg/kg/dia de isoflavonas ao longo da gestação e lactação. O grupo controle foi mantido somente com a dieta isenta de soja e alfafa. Na desmama, foram avaliados o peso e a morfologia dos órgãos do aparelho reprodutor e os níveis séricos de testosterona de parte dos filhotes machos. O restante deles foi submetido à dieta controle desde a desmama até a fase adulta. Após a puberdade, os animais foram avaliados quanto ao comportamento sexual, qualidade do sêmen e morfologia dos órgãos reprodutivos. No segundo experimento, fêmeas foram alimentadas com as mesmas dietas empregadas no primeiro experimento, porém a suplementação com isoflavonas foi realizada com doses variando de 2,5 a 20 mg/kg/dia. As doses de isoflavonas foram selecionadas com base em estimativas da ingestão de isoflavonas a partir do consumo de alimentos derivados da soja. Após a desmama, os filhotes machos receberam a mesma dieta fornecida para suas respectivas mães até o fim do experimento. Foi avaliado nestes animais a idade à puberdade, qualidade do sêmen e o comportamento sexual, e, na 33ª semana de vida o peso e a morfologia dos órgãos reprodutivos. Os resultados deste estudo foram baseados em dados obtidos da avaliação de 100 machos num período de 3 anos. O número de espermatozóides esteve de acordo com os valores da literatura para coelhos da raça Nova Zelândia e não variou significativamente em relação ao grupo controle, embora o volume de sêmen tenha sido menor em coelhos expostos à alta dose de isoflavonas (20 mg/kg/dia). O peso dos órgãos reprodutivos não diferiu estatisticamente do grupo controle e não houve evidência de malformações genitais, alterações metaplásicas, ou qualquer outra alteração histopatológica correlacionada com os tratamentos. Nos jovens, a análise histológica dos testículos não revelou diferenças no desenvolvimento gonadal. Coelhos suplementados de forma crônica com 20 mg/kg/dia de isoflavonas apresentaram menor ingestão de alimentos e peso corporal na fase adulta. Este achado é economicamente importante na produção animal; todavia os animais alimentados com a dieta contendo soja apresentaram na 33ª semana de idade consumo de alimento e peso corporal maiores em 6 e 4% respectivamente do que os animais do grupo controle (P < 0,05). Apesar dos recentes alertas, os resultados deste estudo não suportam a hipótese de que a exposição à isoflavonas em doses compatíveis com o consumo de alimentos à base de soja possa comprometer a saúde reprodutiva masculina
Abstract: This study was proposed to determine if perinatal (that is gestation and lactation) or chronic exposure to isoflavones trough consumption of soy containing diet or semipurified soy isoflavones may disrupt male reproductive health of rabbits. In the first experiment, groups of dams were fed either soy containing diet or soy and alfafa free diet supplemented with soy isoflavones at levels of 10 and 20 mg/kg/day throughout gestation and lactation. The control group was kept on soy and alfafa free diet only. Reproductive organs weight and morphology and serum levels of testosterone of part of the male offspring were evaluated at weaning. Remaining males were subjected to the control diet from weaning to adulthood. Sexual behavior, semen quality and reproductive organs morphology were evaluated after puberty. In the second experiment, groups of dams were fed same diets employed in the experiment 1, but supplementation with isoflavones were performed with doses ranging from 2,5 to 20 mg/kg/day. Dose levels of isoflavones were selected on the basis of the reported estimative of isoflavones intake from the consumption of soy-based foods. After weaning, male offspring received the same diet, which was given to the respective mother. The age that males reached puberty, semen quality and sexual behavior were evaluated in these animals and at 33 weeks of age reproductive organs weight and morphology were analyzed. Results of this study were sustained by data from the evaluation of 100 males in a period of 3 years. Sperm counts was within literature values for New Zealand rabbits and did not vary significantly in relation to control group, although semen volume has been lesser in rabbits exposed to high levels of isoflavones (20 mg/kg/dia). Reproductive organs weight did not differ statistically from the control, and there was no gross evidence of genital malformations, metaplastic changes, or any histopathologic alteration that was correlated with the treatments. In the young rabbits, histological analysis of the testes did not revel differences in gonadal development. Rabbits chronically supplemented with 20 mg/kg/day of soy isoflavones showed lesser food intake and body weight at adulthood. This find is economically important in animal production; however the animals fed soy containing diet showed food consumption and body weight 6 and 4%, respectively higher than animals of the control group at 33 weeks of age (P <0.05). In conclusion, despite recent alerts, results of this study did not support the hypothesis that isoflavones consumption at dietary levels may impair male reproductive health
Doutorado
Biologia Celular
Doutor em Biologia Celular e Estrutural
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Román, Pérez Erick. "The role of ERa, ERß and phytoestrogens from soy in P53-mediated response to DNA damage in mammary epithelium." Amherst, Mass. : University of Massachusetts Amherst, 2009. http://scholarworks.umass.edu/dissertations/AAI3372274/.
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Thesis (Ph. D.)--University of Massachusetts Amherst, 2009.On title page, the 'a' in ERa is symbolized by the Greek symbol for alpha. Includes bibliographical references (p. 108-124). Print copy also available.
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Verhoog, Nicolette Jeanette Dorothy. "Evaluation of the phytoestrogenic activity of honeybush (Cyclopia)." Thesis, Stellenbosch : University of Stellenbosch, 2006. http://hdl.handle.net/10019.1/2198.
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Thesis (MSc (Biochemistry))--University of Stellenbosch, 2006.The phytoestrogenic activity of Cyclopia, used to prepare honeybush tea, was evaluated and compared with that of the endogenous estrogen, 17-β-estradiol (E2) and the known phytoestrogen, genistein. Phytoestrogens are plant polyphenols much in demand in the nutraceutical market as they mediate an estrogenic effect through binding to estrogen receptor (ER) subtypes, ERα and ERβ.
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Mackinnon, Lorna Jay. "Biomarkers of isoflavone intake : validity at high intakes /." St Andrews, 2007. http://hdl.handle.net/10023/222.
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Lin, Hoi-yan Amanda, and 連凱茵. "The ligand binding properties and non-genomic signaling mechanisms of membrane receptors for estrogen and phytoestrogens." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45152196.
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Joy, Sheeja. "Acute effects of phytoestrogens on nitric oxide synthesis and mitogen activated protein kinases in endothelial cells." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414383.
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Blake, Crystal. "The Effects of Prenatally Administered Phytoestrogens on the Reproductive and Behavioral Development of Long-Evans Rats." BYU ScholarsArchive, 2008. https://scholarsarchive.byu.edu/etd/2364.
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Equol is known to be a selective androgen modulator and has the ability to bind and inhibit 5-alpha dihydrotestosterone (5α-DHT). Equol is also a selective estrogen receptor modulator and is able to bind beta estrogen receptors with high affinity. As estrogen receptors are found in the hypothalamus, pituitary, and gonads, prenatally administered equol could affect the morphological and reproductive development of offspring. To test this hypothesis, during gestational days 14 to 20, forty-two pregnant Long-Evans rats were given one of six treatments: 1) no treatment, 2) injection with dimethyl sulfoxide (DMSO), 3) injection with 10 mg/kg equol, 4) injection with 21.0 mg/kg equol, 5) injection with 63.0 mg/kg equol, or 6) injection with 90.0 mg/kg flutamide. At birth the pups were weighed, anogenital distance measured, and sex was determined. Some of the animals were sacrificed and trunk blood collected from both the mothers and pups. Serum levels of phytoestrogens, estradiol, testosterone, and 5α-DHT levels were determined. Some pups were allowed to grow up to day 29 and were tested on the forced-swim test with the parameters of time mobile, time immobile, swim distance, and average speed measured. The flutamide treated pups had the lowest anogenital distance. The low equol dose animals had the largest anogenital distance. There were no significant differences in 5α-DHT serum levels in the male offspring among the treatments. However in non-injected control female offspring displayed significantly lower 5α-DHT levels than all the other groups. Mothers treated prenatally with equol displayed significantly higher circulating equol levels compared to controls values. Rats injected with 63.0 mg/kg of equol gained the least weight during pregnancy. Their offspring also had the lowest body weights at birth. Male and female offspring displayed similar behaviors in the Porsolt forced-swim test among the treatment groups. The low and high equol groups displayed the least depressive-like behaviors. The offspring from mothers treated with the medium and high equol doses both gained the most weight from birth to day 29. Treating pregnant rats with equol during the last week of gestation does not appear to have any affect on morphological genital development of the offspring.
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Mortimer, Morne Francois. "Isolation and identification of compounds conferring phytoestrogenic activity to Cyclopia extracts." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/95748.
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Thesis (MSc)--Stellenbosch University, 2014.ENGLISH ABSTRACT: Phytoestrogens are perceived as a safer alternative to conventional hormone replacement therapy (HRT) for the alleviation of menopausal symptoms as they present a decreased side-effect profile. The Cyclopia subternata (honeybush) methanol extract, SM6Met, displays estrogenic attributes desirable for the development of an phytoestrogenic nutraceutical, namely, estrogen receptor (ER) α antagonism, ERβ agonism, and antagonism of 17β-estradiol (E2)-induced breast cancer cell proliferation. Activity-guided fractionation was employed in an attempt to isolate and identify the compounds inducing the specific estrogenic profile of SM6Met. Fractions were evaluated for estrogenic attributes and major polyphenols present. Initial liquid-liquid fractionation of SM6Met yielded a polar fraction (PF) and a non-polar fraction (NPF), with the estrogenic attributes of interest retained and concentrated in NPF. Subsequent high performance counter-current chromatography (HPCCC) fractionation of NPF yielded three fractions (F1-F3). Interestingly, the fractions revealed separation of the previously demonstrated positive estrogenic attributes of NPF into separate fractions, with F1 and F2 acting as ERα antagonists, only F2 inducing antagonism of E2-induced breast cancer cell proliferation and only F3 retaining ERβ agonist activity. Although ERβ agonism displayed by F3 was robust and significantly higher than that of 10-11 M E2, it also displayed weak ERα agonism. Fractionation also for the first time in the study revealed ERβ antagonism, as induced by F1. In terms of major polyphenols HPCCC fractionation resulted in a divergence with F1 emerging as the dihydrochalcone-rich fraction and F2 as the flavanone and benzophenone-rich fraction, while the xanthones, flavones and phenolic acids were retained in F3. In addition, a preliminary absorption study was conducted using the ex vivo flow-through diffusion assay whereby the permeability of porcine small and large intestine for polyphenols in SM6Met was evaluated. The major compounds present in SM6Met were not able to penetrate the large intestinal mucosa, but small intestinal permeation of all major compounds in SM6Met ensued, with apparent permeability coefficient (Papp) values ranging from 1.91-3.74 x 10-6 cm.s-1, indicative of good intestinal absorption. Open source programs used for theoretical prediction of absorption gave conflicting results, emphasising the need to confirm predictions experimentally. ACD/Labs predicted poor intestinal absorption of SM6Met compounds based on physicochemical profiling, while OSIRIS and ChemAxon anticipated good absorption. In conclusion, activity-guided fractionation results suggest that retention of all the positive estrogenic attributes of the original SM6Met in one fraction is not an attainable goal. This suggests that several of the polyphenols present in SM6Met or NPF, through antagonistic, synergistic, or additive effects, may together be conferring these desired estrogenic traits. Thus production or isolation of a mixture of compounds, i.e. an “intelligent” mixture, should serve as a superior strategy in designing a nutraceutical product tailored to user demand of estrogenic activity.
AFRIKAANSE OPSOMMING: Fitoestrogene word beskou as ‘n veiliger alternatief vir konvensionele hormoon-vervangingsterapie (HVT) vir die verligting van simptome geassosiaeer met menopause aangesien dit ‘n verminderde newe-effek profiel vertoon. Die metanol ekstrak van Cyclopia subternata (heuningbos), SM6Met, vertoon estrogeniese eienskappe wat wenslik is vir die ontwikkeling van ‘n fitoestrogeen nutraseutiese middel, naamlik, estrogeen reseptor (ER) α antagonisme en ERβ agonisme, asook antagonisme van 17β-estradiol (E2) geïnduseerde proliferasie van borskankerselle. Aktiwiteit-begeleide fraksionering (ABF) is gebruik om die verbindings wat die spesifieke estrogeniese profiel aan SM6Met verleen te probeer isoleer en identifiseer. Fraksies is ge-evalueer vir estrogeniese eienskappe, asook vir die hoof polifenole teenwoordig. Aanvankilike vloeistof-vloeistof fraksionering van SM6Met het ‘n polêre fraksie (PF) en ‘n nie-polêre fraksie (NPF) opgelewer met behoud en konsentrering van die wenslike estrogeniese eienskappe in NPF. Daaropeenvolgende hoë werkverrigting teen-vloei chromatografie (HPCCC) van NPF het drie fraksies (F1-F3) opgelewer. Interessant genoeg het hierdie fraksies ‘n verdeling van die wenslike estrogeniese eienskappe van NPF in die individuele fraksies teweeggebring, deurdat F1 en F2 ERα antagonisme getoon het, F2 E2-geïnduseerde proliferasie van borskankerselle antagoniseer het, en net F3 ERβ agonis-aktiwiteit behou het. Alhoewel die ERβ agonis-aktiwiteit van F3 betekenisvol hoër was in vergelyking met die aktiwiteit van 10-11 M E2, het dit ook swak ERα agonisme getoon. Verder het fraksionering, vir die eerste keer in hierdie studie, ERβ antagonisme meegebring soos getoon deur F1. HPCCC het ook ‘n skeiding van die hoof polifenole veroorsaak, waarvolgens F1 as die dihidrogalkoon-ryke fraksie, F2 as die bensofenoon-ryke en flavanoon-ryke fraksie, en F3 as die xantoon-, flavoon- en fenoliese suur-ryke fraksie tevoorskyn gekom het. ‘n Voorlopige absorpsie studie, wat gebruik gemaak het van die ex vivo deurvloei diffusie toetssisteem, is uitgevoer om die deurlaatbaarheid van vark dik- en dunderm vir SM6Met polifenole te evalueer. Die hoof verbindings van SM6Met kon nie die dikderm mukosa penetreer nie, maar die deurlaatbaarheid van die dunderm vir alle SM6Met hoof polifenole is aangetoon, met skynbare deurlaatbaarheidskoëffisiënt (Papp) waardes wat strek vanaf 1.91 tot 3.74 x 10-6 cm.s-1, ooreenstemmend met goeie intestinale absorpsie. Oopbron programme, wat gebruik is vir die teoretiese voorspelling van absorpsie deur gebruik te maak van fisiese-chemiese profilering van verbindings, het teenstellende resultate opgelewer wat daarop dui dat hierdie voorspellings eksperimenteel bevestig moet word. ACD/Labs, wat van die fisiese-chemiese eienskappe van die verbinding gebruik maak, het swak intestinale absorpsie van die polifenole voorspel, terwyl OSIRIS en ChemAxon goeie absorpsie voorspel het. Ten slotte, resultate van aktiwiteit-begeleide fraksionering het getoon dat behoud van al die gewensde estrogeniese eienskappe van SM6Met in een fraksie nie ‘n haalbare doelwit is nie. Hierdie bevinding dui daarop dat verskeie van die polifenole teenwoordig in SM6Met of NPF saam, deur middel van antagonistiese, sinergistiese of additiewe effekte, die wenslike estrogeniese eieskappe verleen. Die ontwikkeling of isolering van ‘n mengsel van verbindings, met ander woorde ‘n ―intelligente‖ mengsel is dus ‘n beter strategie vir die ontwerp van ‘n estrogeniese nutraseutiese produk om die verbruikers-aanvraag van estrogeniese aktiwiteit te voorsien.
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Casey, Karen Julia. "The long term effects of high intake of soya phytoestrogens on bioavailability metabolism and excretion of isoflavones." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414003.
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Jones, Emily. "The Effects of Dietary Phytoestrogens on Waist-to-Hip and Waist-to-Height Ratios in Prepubescent Girls." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1276947568.
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Roostaei, Davoud. "Isolation and characterisation of anti-diabetic pharmacological activities of phytoestrogens and components of Moringa peregrina (Forssk) Fiori." Thesis, London Metropolitan University, 2015. http://repository.londonmet.ac.uk/1141/.
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Diabetes is an endocrine disease characterised by a chronic increase in blood sugar levels caused by a deficiency of insulin production, which leads to type 1 diabetes, or by a loss of tissue response to insulin, which leads to type 2 diabetes. The disease leads to disruption of metabolism, vascular damage and damage to the nervous system, as well as damage to other organs and systems. Type 2 diabetes is becoming more common throughout the world, due to poor nutrition and lifestyle, and genetic background. Efforts have accordingly been increased towards developing and refining treatments as well as to addressing the underlying causes of the disease. Many parts of the world have a documented history of the use of plants to treat diabetes, and these can be an attractive, local, alternative to expensive pharmaceutical medicines. Accordingly there is an increasing interest in identifying new phytochemicals with proven pharmacological effects on diabetes. The tree Moringa peregrina is commonly found throughout the Middle East and the oil from its seeds has been used for thousands of years. Other members of the Moringa family have recorded anti-diabetic family and Moringa peregrina was chosen for investigation in this work with the aim of characterising anti-diabetic activity from its leaves. Six extracts were prepared using solvents water, methanol, butanol, ethyl acetate, chloroform and hexane, based on standard extraction techniques. The study was designed to assess the effect of these six extracts on the uptake of glucose in a human hepatoma cell line (HepG2) using a well-studied fluorescent derivative of glucose, 2-2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino glucose (2-NBDG). The cells can take up 2-NBDG instead of glucose via glucose transporters and its uptake is indicative of the capacity of cells to take up glucose, i.e. of the number of active glucose transporters on the cell surface. The results revealed that the extracts prepared with ethyl acetate and chloroform increased glucose uptake significantly more than the other extracts. Moreover the effects of the extracts were rapid, with a one hour treatment producing a similar stimulation to a 24 hour treatment. These data were confirmed in a second method of investigation of the hypoglycaemic effect of the extracts, by measuring consumption of glucose from cell culture medium. A preliminary assessment of the effect of active extracts on expression of the main glucose transporter of HepG2 cells, GLUT1, by western blotting indicated no large changes in expression. Dietary phytoestrogens have been shown to play a beneficial role in obesity and diabetes, so the second part of this study investigated the effect of phytoestrogens on glucose uptake. Three phytoestrogens (daidzein, formonontein and genestin, which are naturally occurring isoflavones) were chosen. HepG2 cells showed a significant increase in glucose uptake after treatment with phytoestrogens compared to the control. In an attempt to identify the active phytochemicals that could account for the observed effects, extensive purification and characterisation of components from the ethyl acetate fraction was undertaken. Seven components were identified: (1) OEthyl 4-[(α-L-rhamnosyloxy)benzyl] thiocarbamate (E), (2) O-Butyl 4-[(α-Lrhamnosyloxy)benzyl] thiocarbamate (E), (3) 4-(α-L-Rhamnosyloxy)benzyl isothiocyanate, (4) ȕ-Sitosterol, (5) Daucosterol, (6) γ’-methyl-quercetin-3-Orutinoside (also known as isorhamnetin-3-O-rutinoside), (7) Rutin. In a final analysis an attempt was made to assess the effect of a representative set of three out of the seven components on basic metabolic activity of HepG2 cells using a Seahorse XF-24 analyser. The three components chosen were O-ethyl 4-[(α-L-rhamnosyloxy) benzyl] thiocarbamate (E), ȕ-sitosterol from the phytosterols family and Rutin. Real-time monitoring of cell metabolism by a Seahorse XF-24 auto analyser after two hours incubation with the three chosen compounds revealed that maximal respiration, non-mitochondrial respiration and spare respiratory capacity have trended towards an increase with ȕ-sitosterol and3-O-ethyl 4-[(α-Lrhamnosyloxy) benzyl] thiocarbamate (E) treatments compared to control. As no similar trends were observed in ATP production, the increased maximal respiration could increase metabolic activity at higher concentrations of glucose and account, in part for the effects observed on glucose consumption.
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Dagdemir, Aslihan Seda. "Paysage épigénétique du cancer du sein." Thesis, Clermont-Ferrand 1, 2014. http://www.theses.fr/2014CLF1MM14/document.
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Le cancer du sein reste la principale cause de décès par cancer chez les femmes et est connu pour la divergence des comportements cliniques et des résultats pour les patientes, malgré les caractéristiques histopathologiques courantes au moment du diagnostic. Cela s'explique par la grande hétérogénéité histologique et moléculaire de la maladie, qui rend difficile le choix d'une thérapie adaptée à chaque patient.L'épigénétique se rapporte aux modifications du phénotype et de l'expression génique. Les modifications épigénétiques du génome peuvent être acquises de novo et sont potentiellement héritées. Les mécanismes épigénétiques agissent pour modifier l'accessibilité de la chromatine à la régulation de la transcription localement et globalement via des modifications de l'ADN et par des modifications ou des réarrangements de nucléosomes. L'épigénétique consiste en plusieurs mécanismes moléculaires: modifications de l'histone, petits ARN non codants ou anti-sens et méthylation de l'ADN étroitement interconnectés.L'incidence et la mortalité par cancer du sein sont plus élevées (incidence environ trois fois supérieure) dans le monde occidental que dans les pays d'Asie avec des différences régionales dans les pays occidentaux. Plusieurs études impliquant des immigrés des pays occidentaux suggèrent que le mode de vie et l'alimentation sont deux des causes principales de ces différences. Un apport alimentaire élevé en phytoestrogènes, principalement sous forme de produits à base de soja, peut produire des taux circulants de phytoestrogènes à effets œstrogéniques. Des études épidémiologiques et expérimentales suggèrent qu'un régime alimentaire riche en phytoestrogènes pouvait avoir des effets protecteurs contre sur les affections liées aux œstrogènes, telles que le cancer du sein.Sur la base de ces informations, nous avons étudié les effets du traitement par les phytoestrogènes; génistéine, daidzéine et 17-β-estradiol sur la modification post-traductionnelle des histones, telles que la méthylation de la lysine et l’acétylation des histones H3 et H4 dans des lignées cellulaires du cancer du sein. Nous avons ensuite étudié les effets de l'inhibiteur de la méthylation de l'histone et de l'inhibiteur de l'histone désacétylase sur la triméthylation et l'acétylation de l'histone-lysine dans les lignées cellulaires du cancer du sein. Nous avons utilisé deux lignées cellulaires de cancer du sein, MCF-7 et MDA-MB-231, chacune traitée respectivement avec de l'hydrochlorure de 3-désazanule (DZNep) [5 µM] (HMTi), du butyrate de sodium (NaBu) [2 mM] (HDACi) et de l'acide de type Suberoylanilide Hydroxamic (SAHA) [1 µM] (HDACi). Enfin, nous avons mené des études sur toutes les lignées cellulaires atteintes de tumeurs du sein afin d'évaluer l'immunoprécipitation de la chromatine (PIP) de certaines modifications de l'histone dans le cancer. Les niveaux relatifs de trois histones modifiées, y compris H3K27me3 (histone 3 Lysine 27 méthylation), H3K9ac (Histone 3 Lysine 9 acétylation) et H3K4ac (Histone 3 Lysine 4 acétylation) seront déterminés dans les tumeurs du sein par rapport au tissu normal correspondant selon le classement de Saint-Gall. Aujourd'hui, ChIP a été couplé à des puces à ADN de promoteur afin d'évaluer les mécanismes de régulation du gène humain à l'échelle du génome. La technologie de la puce sur puce pourrait être utilisée pour étudier les altérations de l'expression globale des gènes dans la tumorigenèse. Ici, nous avons étudié les gènes exprimés de manière différentielle associés aux histones modifiées H3K27me3, H3K9ac et H3K4ac dans les tumeurs du sein à l'aide de microréseaux Agilent SurePrint G3 400kX2 contenant environ 21 000 transcrits humains. Nous analyserons les régions enrichies de chaque promoteur de gène dans trente tumeurs du sein par rapport à des échantillons de tissus normaux. Les échantillons de tumeurs du sein seront classés en fonction de leur profil clinique, en particulier du statut des récepteurs hormonauxBreast cancer remains the leading cause of cancer-related deaths in women, and is noted for conflicting clinical behaviors and patient outcomes, despite common histopathological features at diagnosis. This can be explained by the high histological and molecular heterogeneity of the disease, making it hard to choose a therapy adapted uniquely to each patient. Epigenetics refer to changes in phenotype and gene expression. Epigenetic modifications of the genome can be acquired de novo and are potentially inherited. Epigenetic mechanisms work to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modifications or rearrangements of nucleosomes. Epigenetics consist in several molecular mechanisms: histone modifications, small non-coding or antisense RNAs and DNA methylation that are closely interconnected. The incidence and mortality of breast cancer is high in the Western world as compared with countries in Asia. There are also differences in the regional cancer incidence rates in Western countries. Several studies involving immigrants to Western countries suggest that lifestyle and diet are two of the main causes of these differences. In Eastern countries, the incidence of breast cancer is approximately one-third that of Western countries, whilst their high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have estrogenic effects. An increasing number of epidemiological and experimental studies have suggested that the consumption of a 4 phytoestrogen-rich diet may have protective effects on estrogen-related conditions, such as breast cancer.Based upon this information, we studied the effects of treatment phytoestrogens; genistein, daidzein and 17-β-estradiol on the post-translational modification of histones such as lysine methylation and acetylation of histones H3 and H4 in breast cancer cell lines. Subsequently, we studied the effects of histone methylation inhibitor and histone deacetylase inhibitor on histone lysine trimethylation and acetylation in breast cancer cell lines. For this study, we used two breast cancer cell lines MCF-7 and MDA-MB-231. Each cell line was treated respectively with 3-Deazaneplanocin A hydrochloride (DZNep) [5 μM] (HMTi), Sodium Butyrate (NaBu) [2 mM] (HDACi) and Suberoylanilide Hydroxamic acid (SAHA) [1 μM] (HDACi) for 48 hours. Finally, we completed studies in all cell lines with breast tumors to assess Chromatin ImmunoPrecipitation (ChIP) of selected histone modifications in cancer. The relative levels of three modified histones, including H3K27me3 (Histone 3 Lysine 27 Methylation), H3K9ac (Histone 3 Lysine 9 Acetylation), and H3K4ac (Histone 3 Lysine 4 Acetylation) will be determined in breast tumors compared to matched normal tissue according to the classification of Saint Gallen. Today, ChIP has been coupled with promoter DNA microarrays to evaluate the mechanisms of human gene regulation on a genome-wide scale. ChIP-on-chip technology could be used to investigate the alterations of global gene expression in tumorigenesis. Here, we investigated differentially expressed genes associated with modified histones H3K27me3, H3K9ac and H3K4ac in breast tumors by Agilent SurePrint G3 400kX2 microarrays containing approximately 21,000 of human transcripts. We will scan the enriched regions at each gene promoter in thirty breast tumors compared with normal tissue samples. Breast tumor samples will be classified according to their clinical profiles, especially hormone receptor status
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Heldring, Nina. "Molecular basis of estrogen receptor antagonism /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-634-4/.
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Chen, Lijuan. "Countercurrent chromatography (CCC), CCC/MS and LC/MS techniques in studies of phytoestrogens in plant extracts and human urine." Thesis, Swansea University, 2004. https://cronfa.swan.ac.uk/Record/cronfa43204.
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Phytoestrogens are members of classes of polyphenolic compounds synthesized by plants. They include isoflavones and other flavonoids, lignans, coumestanes and zearalenones. Photoestrogens are weak estrogen-like plant compounds that act similarly to the hormone estrogen, Over the last twenty years, interest in the physiological effects of phyto-estrogen containing plant substances has increased significantly, since it was demonstrated that the phytoestrogen components may play a potential role in the prevention and treatment of hormonally-dependent diseases, including breast and prostate cancer. This thesis describes studies of High Speed Countercurrent Chromatography and combined Liquid Chromatography-Mass Spectrometry techniques in the separation, purification, identification and quantitation of phytoestrogens in plants and human fluid. Chapter One provides a brief history and introduction to the principles and applications of high-speed countercurrent chromatography, liquid chromatography, mass spectrometry, and their combination of interfacing systems. Chapter Two investigates the separation and purification the flavonoids from the ethyl acetate extract from the seeds of O, indicum using high-speed countercurrent chromatography. Five flavonoids are successfully separated and purified with high purities (above 92 %) and two components are for the first time separated and identified from the plant. Mass spectrometry, Ultraviolet and Nuclear Magnetic Resonance are used for the structural elucidations of flavonoids. Chapter Three and Chapter Four compare different coil volumes of high-speed countercurrent chromatography instruments in the separation and purification of phytoestrogens. On line high speed countercurrent chromatography-mass spectrometry is studied for the separation and identification of flavones and isoflavones in plants. Chapter five develops a simple and accurate method for the quantitative determination of phytoestrogens in soy food supplements using on line liquid chromatography-mass spectrometry. Nine isoflavones are determined and liquid chromatography-tandem mass spectrometry is also investigated to the structural elucidation of some unknown components. Chapter Six develops a sensitive on line liquid chromatography-mass spectrometry method to determine the concentration of isoflavones and their major metabolites in human urine after consumption of soy-based supplements. The structural elucidations of some unknown metabolite isoflavones are also explored using liquid chromatography-tandem mass spectrometry.
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Botelho, Marta Alexandra Ferreira Marques. "Fitoestrogénios na égua lusitana: efeito do cumestrol na síntese da prostaglandina F2α’ no endométrio." Master's thesis, ISA/UTL, 2012. http://hdl.handle.net/10400.5/5300.
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Mestrado em Engenharia Zootécnica - Produção Animal - Instituto Superior de Agronomia / Faculdade de Medicina VeterináriaPhytoestrogens are compounds found in plants and, consequently, in animal feed, whose similarity with 17β-estradiol (E2) enables its binding to estrogen receptors influencing several endocrine mechanisms during the oestrous cycle. This study shows that coumestrol can influence the secretory function of the endometrium of the mare, modulating the production of prostaglandin F2α (PGF2α). Coumestrol was found in clover mixed pastures and in alfalfa pellets used to formulate a controlled diet. This phytoestrogen and its metabolite were also quantified in blood plasma of non-pregnant Lusitano mares showing its absorption, after ingestion. In in vitro experiments, the effect of coumestrol on PGF2α secretion from equine endometrial epithelial and stromal cells was examinated. Cells were stimulated with coumestrol (10-8M), E2 (10-9M) and oxytocin (OT,10-7 M, positive control) for 24 hours. Coumestrol increased viability of stromal cells (p<0.05), transcription of the gene responsible for prostaglandin sinthase - 2 in the same cells (p<0.05) and the secretion of PGF2α in both epithelial (p<0.001) and stromal (p<0.001). These findings suggest that coumestrol may modulate prostaglandin secretion from endometrial cells and may be potentially associated to oestrus disorders in the mare.
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Thai, Quoc Dang. "Etude phytochimique de deux espèces de Platanaceae européennes Platanus acerifolia (France) et Platanus orientalis (Grèce)." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05P607.
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Le platane est un arbre de la famille des Platanaceae très commun en ville en particulier en Europe et dans toutes les zones tempérées. Les espèces du genre Platanus et plus particulièrement l’espèce Platanus orientalis, très répandue en Grèce, sont sévèrement attaquées par des agents phytopathogènes provoquant le chancre coloré du platane, l’anthracnose ou l’oïdium. En revanche, Platanus acerifolia, un hybride obtenu entre P. occidentalis and P. orientalis, très commun en France, se montre plus résistant vis-à-vis de ces pathogènes. L’étude par HPLC d’extraits de deux espèces de Platanaceae européennes P. acerifolia et P. orientalis a montré des différences selon le solvant d’extraction. L’extrait dichlorométhanique de P. acerifolia s’est montré plus riche en composés que l’espèce P. orientalis. Par contre, les chromatogrammes obtenus à partir des extraits méthanoliques sont très similaires et dominés par les deux composés majoritaires (tiliroside et platanoside). Des techniques préparatives comme la chromatographie de partage centrifuge (CPC), la moyenne pression (MPLC), la chromatographie sur colonne de Sephadex ou sur résine XAD-7 ont été utilisées afin d’isoler les différents constituants majoritaires et d’identifier les composés qui diffèrent d’une espèce à l’autre. L’élucidation structurale est réalisée grâce à des techniques telles que HR-EIS-MS et RMN 1D & 2D. L’étude de l’extrait dichlorométhanique nous a permis de compléter la connaissance phytochimique de ces deux plantes européennes et a conduit à l’isolement et à la détermination structurale de 38 molécules dont 7 composés nouveaux (1 coumarine, 3 flavonols prenylés, 2 dihydrochalcones, un terpénoïde. Par ailleurs, l’extrait méthanolique a conduit d’une part à l’isolement du tiliroside et du platanoside majoritaires et d’autre part à l’isolement de composés minoritaires, trente-trois autres molécules dont 5 nouveaux composés (1 flavonol glucosylé, 3 coumarines, 1 dihydrochalcone). Enfin, l’évaluation biologique des composés isolés in vitro ou in vivo a été réalisée sur différentes cibles : activités antifongiques, anti-âge, antioestrogéniques. Les activités cytotoxiques sur les cellules de cancer du sein MCF-7 et sur les cellules de cancer de l’endomètre (ISHIKAWA)Platanus is a small genus of trees belonging to Platanaceae family, very common in Europe and temperate zones. Platanus species, and especially Platanus orientalis (Oriental plane), wide-spread in Greece are known to be severely attacked by phytopathogens such as Ceratocystis fimbriata f. sp. platani for canker stain, Apiognomonia veneta for anthracnose and Microsphaera platini for powdery mildew. However Platanus acerifolia (London plane), a hybrid between the P. occidentalis and P. orientalis, which is very common in France, have been found to be resistant to these pathogenic fungi. The HPLC profile of the dichloromethane extracts of the two species P. orientalis and P. acerifolia revealed a qualititative difference whereas, the methanol extracts were found to be similar with two predominant phenolic constituents (tiliroside and platanoside) present in both species. Further isolation and purification of their secondary metabolites were performed using various chromatographic techniques (CPC, MPLC, CC, XAD-7, Sephadex LH20, prep-TLC) and their identification was performed by HRMS and NMR (1 & 2D) spectroscopy. The studies of dichloromethane extract allowed us to deal with phytochemical knowledge of these two European plants in depth and led to isolation and structural elucidation of 38 compounds including 7 news constituents (1 coumarin, 3 flavonols, 2 dihydrochalcones and 1 terpenoid). Moreover, the methanol extract led to the isolation of their major constituents (tiliroside and platanoside) in one step. Furthermore, 33 minors compounds were isolated including 5 news compounds (one flavonol glycoside 3 coumarins and 1 dihydrochalcone). In addition, the isolated compounds have been subjected to in vitro or in vivo evaluation on different targets: antifungal, anti-ageing, anti-oestrogenic properties. Finally, the cytotoxic activity was studied on breast cancer cells (MCF-7) and endometrial cancer (Ishikawa)
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Sandhu, Kiran Veer Kaur [Verfasser], and Oliver [Akademischer Betreuer] Stork. "Modulation of social and emotional behaviors by glutamic acid decarboxylase (GAD) and phytoestrogens / Kiran Veer Kaur Sandhu. Betreuer: Oliver Stork." Magdeburg : Universitätsbibliothek, 2014. http://d-nb.info/1066295328/34.
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