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Tucker, Heather Ashley. "Factors affecting estrogen excretion in dairy heifers." Thesis, Virginia Tech, 2009. http://hdl.handle.net/10919/34362.
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Two studies were conducted to assess factors affecting estrogen excretion in dairy heifers. The objective of the first study was to quantify estrogenic activity in feces and urine during the estrous cycle. Ten non-pregnant Holstein heifers were fed the same diet for 28 d. Plasma, feces, and urine samples were collected daily. Plasma 17-β estradiol (17-β E2) was quantified with RIA and used to confirm day of estrous. Feces and urine samples from days -12, -6, -2, -1, 0, 1, 2, 6, 12 of the estrous cycle were analyzed with RIA and Yeast Estrogen Screen (YES) bioassay. Plasma 17-β E2 concentrations peaked on day of estrus, with feces and urine estrogenic excretion peaking a day after. The objective of the second study was to quantify variation in estrogenic activity in feces and urine due to increased dietary phytoestrogen content. Ten Holstein heifers were randomly assigned to treatment sequence in a two-period crossover design. Dietary treatments consisted of grass or red clover hay, and necessary supplements. Feces and urine samples were collected and pooled for analysis. Estrogenic activities of pooled samples were quantified using the YES bioassay. Estrogenic excretion in feces and urine was higher for heifers fed red clover hay. Fecal and urine samples from five heifers were analyzed using LC/MS/MS to quantify excretion of phytoestrogenic compounds. Heifers fed red clover hay excreted more equol than heifers fed grass. Identifying sources of variation in estrogenic activity of manure will aid in the development of practices to reduce environmental estrogen accumulation.Master of Science
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Brown, Greta Suzanne. "The Effects of Estrogen on the Growth and Tuberization of Potato Plants (Solanum tuberosum cv. 'Iwa') Grown in Liquid Tissue Culture Media." Thesis, University of Canterbury. Biological Sciences, 2006. http://hdl.handle.net/10092/1376.
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Mammalian estrogens and estrogen-like compounds known as xeno-estrogens are being found in and excreted into the environment in ever increasing amounts. The xeno-estrogen DDE has been found at high concentrations of 1-5 mg/kg of soil (Aislabie et. al, 1997). These estrogens and xeno-estrogens are having a devastating effect on animal-life, yet little is known or understood on the effects of estrogens on plant-life. Thus it is important to determine what effects (if any) estrogens may have on plants. Other research has shown that estrogen has an effect on plants grown in vitro (Janeczko and Skoczowski, 2005). This research aims to help increase the amount of information on what effects estrogens may have on plants. In this study, the effects of mammalian estrogens (17-β-estradiol, estrone and estriol) on the growth and tuberization of potato plants (Solanum tuberosum L. cv 'Iwa') grown in liquid tissue culture medium are presented. It was found that at even 0.1 mg/L of estrogen, root growth of the plants was diminished and at 10 mg/L of estrogen, plant deformity was apparent and callus growth induced. Acid phosphatase activity of the plants was increased with the addition of 0.1 mg/L and 1 mg/L of estrogen but then decreased with the addition of 10 mg/L of estrogen. Tuber production was slightly reduced in plants treated with estrogen compared to the control.
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Tan, Eugene You-Chin. "Futile cycling of estrone sulfate and estrone in liver." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ59053.pdf.
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Rocha, Marcela Sene. "Avaliação reprodutiva de ovelhas da raça Texel submetidas a diferentes protocolos de indução de estro na contraestação reprodutiva." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-11042014-114526/.
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Para estudo de diferentes períodos de protocolos de indução do estro e de um novo dispositivo de progesterona para pequenos ruminantes (DPR - Tecnopec, Brasil) foram realizados dois experimentos em ovelhas da raça Texel durante a contraestação reprodutiva. Experimento 1: com o objetivo de comparar a eficiência de protocolos de indução do estro em períodos de nove versus doze dias e com a utilização de dispositivos novos versus usados através das taxas de gestação e manifestação de estro, foram utilizados 160 ovelhas Texel. Os animais foram divididos aleatoriamente em 4 grupos: protocolo de 9 dias com a utilização de um dispositivo feito em silicone novo (G9N, n=91), protocolo de 9 dias com a utilização de dispositivo usado (G9U, n=25), protocolo de 12 dias com a utilização de dispositivo novo (G12N, n=26) e protocolo de 12 dias com a utilização de dispositivo usado (G12U, n=18). Os dispositivos foram colocados no dia zero (D0) e retirados no dia nove (D9) nos grupos G9N e G9U e doze dias após (D12) nos grupos G12N e G12U. Junto com a aplicação de 0,125mg de cloprostenol (Estron, Agener, Brasil) e 500UI de eCG (Folligon®, Intervet, Netherland). Experimento 2: com o objetivo de comparar o Dispositivo Pequenos Ruminantes (DPR - Tecnopec, Brasil) versus esponja impregnada com medroxiprogesterona Progespon® (MSD, Brasil) no protocolo de 9 dias foram utilizadas 152 ovelhas Texel. Os animais foram divididos aleatoriamente em 2 grupos: protocolo de 9 dias com a utilização da esponja Progespon® (GP, n=61) e protocolo de 9 dias com a utilização do Dispositivo Pequenos Ruminantes (GDPR, n=91). O protocolo utilizado foi semelhante ao G9N do experimento 1 exceto pelo tipo de dispositivo utilizado. No experimento 1 e 2 as variáveis analisadas foram: taxas de manifestação de estro, concepção e prenhez e dispersão no intervalo de cio. O exame de ultrassonografia para detecção de prenhez (Chisson, KYLUMAX) foi realizado com 30 e 60 dias da retirada do dispositivo. O delineamento utilizado foi inteiramente casualizado e os dados analisados através do programa SAS System for Windows (SAS, 2000). Como resultados observou-se que não houve diferenças entre os protocolos de 9 e 12 dias, assim como entre os dois tipos de dispositivos em relação a taxa de manifestação de estro, concepção e prenhez. Houve maior taxa de manifestação de estro (P<0,05)) do dispositivo novo se comparado com o usado. Foi observado menor (P<0,05) dispersão na ocorrência de estro no protocolo de 9 dias utilizando o dispositivo novo. Conclui-se que os protocolos de 9 e 12 dias e ambos dispositivos são semelhantes quanto a eficácia de indução do estro em ovelhas Texel durante a contraestação reprodutiva e que o dispositivo novo apresenta maior taxa na manifestação de estro em comparação com o dispositivo usado.Two experiments were conducted to study different periods of estrus induction and study of a new progesterone device for small ruminants (DPR - Tecnopec, Brazil) protocols in Texel ewes during the non-breeding season. Experiment 1: 160 Texel ewes were used in order to compare the efficiency of estrus induction protocols with the nine versus twelve days periods and the use of new versus used devices through the rates of estrus manifestation and pregnancy. The animals were randomly divided into 4 groups: 9 days protocol with the use of the new device (G9N, n = 91) and 9 days protocol with the use of used devices (G9U, n = 25) 12 days protocol with the use of the new device (G12N, n = 26) and 12 days protocol with use of used device (G12U, n = 18). The devices were placed on day zero (D0) and removed on day nine (D9) in the G9N and G9U groups and twelve days after (D12) in the groups G12U and G12N, together with the use of 0.125 mg of cloprostenol (Estron, Agener, Brazil) and 500 IU of eCG (Folligon®, Intervet, Netherland). Experiment 2: 152 Texel ewes were used in order to compare the Small Ruminants Device (DPR - Tecnopec, Brazil) versus Sponge impregnated with medroxyprogesterone Progespon® (MSD, Brazil) in the 9 days protocol. The animals were randomly divided into 2 groups: 9 days protocol using sponge Progespon® (GP, n = 61) and 9 days protocol using Small Ruminants Device (GDPR, n = 91). The protocol used was similar to that G9N of experiment 1 except by the type of device used. 312 sheep were used in the period of September to November 2012. The considered methodologies in experiment 1 were: rates of estrus manifestation, conception and pregnancy and dispersion in the heat interval. The ultrasound examination for detection of pregnancy (Chisson, KYLUMAX) was performed at 30 and 60 days after D9 and D12. The experimental design was completely randomized and analyzed using the SAS System for Windows (SAS, 2000) program. As results it was shown no differences between the protocols 9 and 12 days, as well as between the two types of devices in relation to the estrus manifestation, conception and pregnancy rate. There was a higher estrus manifestation rate (P <0.05) of the new device compared with the used one. It was observed lower (P <0.05) dispersion in the occurrence of estrus in the 9 days protocol. We conclude that the protocols 9 and 12 days and both devices are similar in efficacy to induce estrus in Texel ewes during the non-breeding season and the new device has the highest rate of estrus manifestation compared to the used device.
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Stowell, Cheri L. "Studies on the mechanism of estrone sulfatase." [Bloomington, Ind.] : Indiana University, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3240028.
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Thesis (Ph. D.)--Indiana University, Dept. of Chemistry, 2006."Title from dissertation home page (viewed July 16, 2007)." Source: Dissertation Abstracts International, Volume: 67-10, Section: B, page: 5732. Adviser: Theodore Widlanski.
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Ray, Peter Christopher. "Studies in ring D fragmentation of estrone." Master's thesis, University of Cape Town, 1998. http://hdl.handle.net/11427/17964.
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Includes bibliographical references.Studies have been conducted in synthesising 14-allyl 19-norsteroids. The eventual aim is to convert the 14-allyl derivatives into bridge-functionalised 19-norsteroids. Two approaches were investigated, with the immediate aim of generating fragmentation intermediates suitable for 14-allylation. The approaches were based on cleavage of the 16,17-bond via oxidative cleavage or fragmentation methodology. The oxidative cleavage routes involved the preparation of 3-methoxy-17 –methylestra-1,3,5(10), 16-tetraen-15-one, which was shown not to undergo regioselective 14-methylation. In an alternative approach 3-methoxy-17a-methylestra-1,3,5(10),14tetraene- 16β, 17β-diol was synthesised. However, the lability of the primary cleaved product prompted synthesis of 3-methoxy-16,17-seco-17a-homoestra-1,3,5(10)-triene16,17a- dione. Chemodifferentiation of the carbonyl groups of the seco derivative provided access to 16-acetoxy-3-methoxy-16, 17-seco-17a-homoestra-1,3,5(10)-trien-17a-one, in an overall yield of 60% from estrone 3-methyl ether. The fragmentation approaches involved conjugate stannylation and silylation of 3-methoxyestra-1,3,5,(10), 15-tetraen-17 -one to give the 15β-trimethylstannyl and 15β-trimethylsilyl 17 -ketones respectively. The stannyl ketone was converted to the 3-methoxy-17a-methyl-15β-trimethylstannylestra-1,3,5,(10)-trien-l7β-ol. Generation of the derived alkoxy radical resulted in formation of 3-methoxy-16, 17-seco-17a-homoestra1,3,5( 10),15-tetraen-17a-one, in low yield, The silyl ketone was converted to the 17acetoxyimino- 3 -methoxy-15β-trimethylsilylestra-l,3,5( 10)-trien, Fragmentation with the borontrifluoride diethyl ether complex resulted in formation of the undesired 3-methoxy13,17-secoestra-l ,3,5(1 0),l4-tetraen-17-nitrile. Since the 15β-trimethylsilyl group did not direct the fragmentation, the 17-acetoxyimino-3-methoxy-16β-trimethylsilylmethylestra-1,3,5(10)-triene was synthesised in the hope that it would be more amenable to silicon directed fragmentation, However, fragmentation with the boron trifluoride diethyl ether complex resulted In formation of the undesired 17-acetoxy-3-methoxy 16β-trimethylsilylmethyl-17a-aza-17a-homoestra-1,3,5(10), 17-tetraene.
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Brito, Ana Marta Mourão de. "Programas de sincronização do estro : diferenças entre duas realidades." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2009. http://hdl.handle.net/10400.5/1251.
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Dissertação de Mestrado Integrado em Medicina VeterináriaOs programas de sincronização do estro em bovinos de leite surgiram como uma ferramenta para auxiliar o progressivo declínio da fertilidade neste sector. Estes programas baseiam-se na utilização de hormonas prostaglandina F2α, hormona libertadora de gonadotropina, progesterona e estrogénios. O principal objectivo do presente trabalho consistiu na análise comparativa dos métodos de sincronização do estro em bovinos de leite, em Greenwich, no estado de Nova York (EUA) e em Hanôver na Alemanha, bem como evidenciar as principais diferenças entre os vários tipos de produção e maneio e a pressão exercida nos protocolos de indução ou sincronização do estro. Nas explorações dos EUA observou-se o uso desequilibrado de programas de sincronização do estro, enquanto a maioria das explorações na Alemanha utilizam fármacos hormonais apenas como tratamento de animais com patologias do foro reprodutivo. A dimensão da exploração, a formação do produtor e o grau de dedicação ao maneio, bem como as características económicas e a legislação relativa ao bem-estar animal, em cada um dos países, revelaram ser os principais factores que determinam a implementação ou não de programas de sincronização do estro numa exploração de bovinos de leite.
ABSTRACT - Estrus synchronization programs in dairy cows emerged as a tool to minimize the progressive fertility decline. These programs are based on hormones such as prostaglandin F2α, gonadotropin releasing hormone, progesterone and estrogens. The main purpose of this work was the comparative analysis of estrus synchronization methods in dairy cows, in Greenwich, state of New York (USA) and in Hannover, Germany, as well as to demonstrate the main differences between the various productions and managements of dairy farms as well as the demands on synchronization protocols. In the USA farms an unfounded way in using synchronization programs was showed, whereas the majority of farms in Germany use drugs mainly as hormonal treatments for animals with reproductive disorders. Farm size, farmers training, and their commitment level to the reproductive management of their farms, as well as the economic and the legislation concerning animal welfare in each country, have proved to be the main factors determining the implementation of estrus synchronization programs in dairy production.
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Afonso, Tiago Sanches Madeira. "Transferência de embriões na égua." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2008. http://hdl.handle.net/10400.5/831.
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Dissertação de Mestrado Integrado em Medicina VeterináriaO objectivo deste trabalho consistiu na aplicação de uma técnica não cirúrgica de transferência de embriões, de forma a aumentar o número da descendência de éguas de genética superior, desde Dezembro de 2007 a Abril de 2008. O estudo foi realizado em dois locais diferentes (A e B). No local A foi utilizada uma égua dadora de 12 anos e duas éguas receptoras de 7 e 8 anos. No local B utilizaram-se cinco éguas dadoras com idades compreendidas entre quatro e 26 anos e seis éguas receptoras com idades de quatro a 15 anos. As dadoras estavam junto com as receptoras, na pastagem. Utilizou-se Prostaglandina F2 para provocar a luteólise e para induzir a ovulação foi utilizada a gonadotrofina coriónica humana, quando se observava um folículo de diâmetro 35 mm e a égua dadora e uma receptora se encontravam nessa situação. Foram efectuadas dez tentativas de recolha de embrião, 7,5 dias após a ovulação, mas apenas se recolheram e transferiram dois embriões. Um dos embriões foi obtido no local A, era um blastocisto expandido e foi classificado com o grau 1. O outro era um jovem blastocisto de grau 3, apresentando um atraso no desenvolvimento, e foi recolhido de uma égua de 26 anos, no local B. No entanto, nenhuma das receptoras ficou gestante.
ABSTRACT The aim of this work was to perform nonsurgical embryo transfers to improve highly genetic mares’ offspring number, since December 2007 until April 2008. The study was carried out at two different farms (A and B). At farm A, a 12 years old donor and two recipients of seven and eight years of age were used. At farm B, five donor mares aging between four and 26 years old and six recipient mares with ages between four and 15 years old were used. Donors and recipients mares were kept together on the pasture. Prostaglandin F2 was used to induce luteolysis and human chorionic gonadotrophin to cause ovulation whenever a follicle 35 mm was simultaneously observed on both the donor and the recipient mare. Ten attempts of embryos recovery were performed at 7.5 days after ovulation but only two embryos were collected and transferred to recipient mares. One embryo (a grade 1 expanded blastocyst) was obtained at farm A, while and a grade 3 early blastocyst with delayed development was collected from a 26 year old donor mare at farm B. However, no pregnancy was sustained after embryo transfer.
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Tanemura, Mai. "The role of estrogen and estrogen receptor β in choroidal neovascularization." Kyoto University, 2005. http://hdl.handle.net/2433/144767.
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Stewart, Ceri Elisabeth. "Estrogen receptor beta and estrogen response in breast cancer cell lines." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491371.
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Ced Stewart: Estrogen receptor beta and estrogen response in breast cancer cell lines Breast cancer affects 1 in 9 women in Britain and its development and treatment are greatly influenced by hormonal status, such as exposure to endogenous estrogen and expression of estrogen receptors (ERs). ERa is an established prognostic marker in breast cancer, but the role of ERp is less certain. The ERs act to regulate gene transcription via a highly complex variety of mechanisms in response to stimuli such as estrogen, tamoxifen or fulvestrant. In order to further define the role of ERp isoforms in breast cancer, their role in the estrogen response must be characterised. This thesis has used a set of four breast cancer cell lines, as well as an MCF7 cell line engineered to over-express ERpl mRNA (MCF7PIx), to investigate the role of ERp in estrogen response. Cells were - treated with a variety of stimuli (estrogen, tamoxifen, fulvestrant, epidermal growth factor and fibroblast growth factor-2) and expression of a panel of ER isoforms, estrogen responsive genes and housekeeping genes was measured using real-time, quantitative PCR. Estrogen response is cell line specific, both in terms of the genes affected and the level of response. These responses can be partly, but not fully, related to the levels of ERa expressed by the cell lines. Expression of individual ER isoforms varies in response to treatment in a time, stimulus and cell line specific manner. Different cell lines vary expression of different subsets of ER isoforms and MCF7pIx, which constitutively over-expresses ERpl mRNA, shows down-regulation of ERpl mRNA expression in response to estrogen. Together these data suggest that regulation may occur at the level of splicing and mRNA stability, as well as at the transcription level. MCF7 and MCF7P Ix showed.remarkably similar responses to treatments. In both cell lines, similar sets of genes were both up- and down-regulated by estrogenic and growth factor treatments. Most -genes showed a similar pattern of transcriptional activation at 0 to 8 h as at 24 h, except for ERpl and ERp2, indicating the importance of control of ERp expression. It was not possible to measure the levels of ERpl protein in the cells, therefore the similarity in responses in MCF7 and MCF7pIx may indicate that, despite the higher levels of ERpl rnRNA, MCF7pIx cells do not overexpress ERPI protein. Measurement of endogenous expression of a set of estrogen responsive genes in a panel of breast cancer cell lines in response to various stimuli has afforded new insights into the levelS and variation in the response achieved in this system. Expression of ERp mRNA was shown to be controlled in a cell line and treatment specific manner, as has previously been shown for ERa. Additionally, it was shown that this regulation was isofonn specific and was maintained when the ERp was overexpressed under the control of an exogenous promoter. This is particularly interesting, as it suggests various levels of regulation, indicating the important role of ERp in downstream estrogen responses. - Supplied by The British Library - 'The world's knowledge'
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Oliveira, Thiago Sardinha de. "Efeitos vasculares promovidos pela estrona em ratas Wistar ovariectomizadas." Universidade Federal de Goiás, 2018. http://repositorio.bc.ufg.br/tede/handle/tede/8868.
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Estrone (E1), the major component of Premarin® and predominant estrogen in postmenopausal women, does not have its vascular effects involving its vasodilatory mechanism of action completely elucidated. Therefore, the aim of this study was to evaluate the effects of E1 treatment on the vascular reactivity of isolated aortic rings and blood pressure in ovariectomized Wistar rats (OVX). For this purpose, 12 week-old Wistar rats were divided into four experimental groups, Sham (physiological estrous rats treated with vehicle), OVX (OVX rats treated with vehicle), OVX + E1 (OVX rats treated with 825μg / kg of E1) and OVX + 17β-estradiol (E2) (OVX rats treated with 15μg / kg of E2). The treatments started after the 8 weeks of surgery trough subcutaneous pathway for 30 days. At the end of treatment, blood pressure measurement by tail plethysmograph was performed. In addition, aortic rings were isolated to evaluate contractile response to phenylephrine (Phe), relaxation to acetylcholine (ACh) or sodium nitroprusside (NPS) by means of concentration curves. The response to ACh in rings previously incubated with superoxide dismutase (SOD), catalase (CAT) or apocynin (NADPH oxidase inhibitor) was also evaluated. The protein expression of SOD, CAT, NOX 1, NOX 2 and NOX 4 were quantified by Western blotting. Follow-up of the weight gain after the OVX or Sham procedure was also performed. After euthanasia, the weight of retroperitoneal fat, uterus and heart were evaluated. E1 treatment decreased body weight and retroperitoneal fat, increased uterine weight, and corrected both the increased blood pressure, and the decreased hyperreactivity to Phe vasoconstrictor agent and also increased endothelium-dependent vasodilatory response to ACh. The effects presented by this hormone are related to compensatory mechanisms in the activity of antioxidant enzymes such as SOD and catalase besides the reduction in the expression of the NADPH oxidase NOX 4 isoform. In addition, E1 reverses the increase in total and LDL cholesterol in the OVX group. Our study confirms the role of oxidative stress in endothelial dysfunction of OVX rats and further demonstrates that E1 reverses elevation of blood pressure and restores endothelial function in OVX rats.
A estrona (E1), componente majoritário do Premarin® e estrogênio predominante na circulação feminina na pós-menopausa, não possui seus efeitos vasculares e mecanismos de ação completamente elucidados. Diante disso, o objetivo do presente trabalho foi avaliar os efeitos do tratamento com E1 em ratas Wistar ovariectomizadas (OVX) sobre a reatividade de anéis de aorta e pressão arterial. Para este estudo, ratas com 12 semanas de idade foram divididas em quatro grupos experimentais, Sham (ratas em estro fisiológico tratadas com veículo), OVX (ratas OVX tratadas com veículo), OVX + E1 (ratas OVX tratadas com 825μg/Kg de E1) e OVX + 17β-estradiol (E2) (ratas OVX tratadas com 15μg/Kg de E2). Os tratamentos foram iniciados após 8 semanas da cirurgia pela via subcutânea pelo período de 30 dias. Ao final do tratamento, foi realizada a medida de pressão arterial por pletismografia de cauda.Além disso, anéis de aorta foram isolados para avaliar resposta contrátil à fenilefrina (Phe), relaxamento à acetilcolina (ACh) ou ao nitroprussiato de sódio (NPS) por meio de curvas de concentração efeito cumulativas. Foi ainda avaliada a resposta à ACh em anéis incubados previamente com superóxido dismutase (SOD), catalase (CAT) ou apocinina (inibidor da NADPH-oxidase (NOX)). A expressão protéica da SOD, CAT, NOX 1, NOX 2 e NOX 4 foi quantificada por Western-blot. Foi realizado o acompanhamento do ganho de peso após o procedimento de ovariectomia nos grupos OVX ou Sham e, após a eutanásia, foi avaliado o peso da gordura retroperitoneal, útero e coração. O tratamento com E1 diminuiu o peso corporal e a gordura retroperitoneal, aumentou o peso uterino, normalizou os níveis de pressão arterial, o aumento da resposta contrátil à Phe e a resposta vasodilatadora dependente de endotélio à ACh. Os efeitos apresentados por este hormônio estão relacionados com mecanismos compensatórios na expressão e atividade de enzimas antioxidantes como SOD e CAT, além da redução na expressão da isoforma NOX 4. Além disso, a E1 reverteu o aumento do colesterol total e LDL observados nas ratas OVX. Os dados apresentados demonstram o papel benéfico da E1 frente ao estresse oxidativo na disfunção vascular, restabelecendo a função endotelial e os níveis fisiológicos da pressão arterial.
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Pettersson, Katarina. "Signal transduction via estrogen receptors (ERs) and estrogen receptor-related receptors (ERRs) /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4184-X/.
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Lee, Chun-lun. "Actions of estrogen and estrogen-related compounds on prostate cancer cell growth /." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38297061.
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Lee, Chun-lun, and 李振倫. "Actions of estrogen and estrogen-related compounds on prostate cancer cell growth." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45011266.
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Karolczak, Magdalena. "Estrogen synthesis and novel mechanisms of estrogen action in the developing brain." Ulm : Universität Ulm, Medizinische Fakultät, 2000. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB9394023.
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Lee, Annie S. (Annie Sang) 1975. "Molecular mechanism of interactions between estrogen receptor and estrogen receptor selective genotoxins." Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/73348.
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Thesis (S.M.)--Massachusetts Institute of Technology, Division of Bioengineering and Environmental Health, 2000.Includes bibliographical references (leaves 43-47).
Although one million new breast cancer cases arise each year worldwide, therapies to treat the disease are limited. Conventional treatments including the chemotherapeutic agent, Tamoxifen, have had only limited success, often showing uncomfortable side effects. Our group has proposed a new scheme for a rational drug design. This scheme utilizes recent findings on the mechanism of cisplatin, the drug found to cure in excess of 93% of all testicular cancer cases. Cisplatin forms DNA adducts that are toxic. The toxicity of these adducts is enhanced by the recruitment of proteins that bind to the adducts and impede adduct repair. This thesis was an attempt to duplicate this "repair shielding" mechanism with another cytotoxin. Specifically, this toxin will be programmed to kill breast cancer cells. Breast cancer cells often overexpress the estrogen receptor protein. By synthesizing a drug that not only binds and damages the DNA but also binds the abundant proteins in the cells, thereby blocking the damaged site from DNA repair proteins, a selective treatment of cancer cells can be achieved. In this study, the human estrogen receptor (hER) and the ligand binding domain of the hER genes were cloned into baculovirus expression vectors, establishing a system where a large quantity of the proteins can be expressed. The proteins expressed in insect cells were purified in one step, using the FLAG-epitope, yielding homogeneous proteins. The proteins were tested for binding to p-estradiol and were confirmed to be functional in ligand binding. They were also tested for their ability to bind the novel drugs synthesized to bind both the protein and the DNA. It was found that the ligand binding domain of the hER was capable of binding the drugs adducted to the DNA. In an effort to elucidate the mechanism of the protein-drug-DNA complex formation, an association experiment was carried out, which showed that the drug more readily bound to the protein than to DNA. However, a significant amount of the drug-protein complex still bound the DNA, if the ratio of the protein to the drug did not exceed 1.5.
by Annie S. Lee.
S.M.
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Andersson, Therése. "Estrogen and Glucocorticoid Metabolism." Doctoral thesis, Umeå universitet, Medicin, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33165.
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Background: Cardiovascular disease (CVD) is the leading cause of death among women in Sweden. The risk of CVD increases rapidly after the menopause. A major contributing factor may be the redistribution of adipose tissue, from the peripheral to central depots, associated with menopause. This change in body composition is commonly attributed to declining estrogen levels but may also be affected by tissue-specific alterations in exposure to other steroid hormones, notably glucocorticoids – mainly cortisol in humans. Indeed, adipose tissue-specific overexpression of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) induces central obesity, insulin resistance and hypertension in mice. Interestingly, estrogen may regulate this enzyme. The aim of this thesis was to investigate putative links between estrogen and glucocorticoid activation by 11βHSD1. Materials and Methods: 11βHSD1 expression and/or activity in adipose tissue and liver, and adipose estrogen receptor α and β (ERα and ERβ) gene expression, were investigated in lean pre- and postmenopausal women and ovariectomized rodents with and without estrogen supplementation. In lean women measures of 11βHSD1 were correlated to risk markers for CVD. The association between adipose 11βHSD1 and ER mRNA expression was investigated in both lean women and rats and in an additional cohort of obese premenopausal women. In vitro experiments with adipocyte cell lines were used to explore possible pathways for estrogen regulation of 11βHSD1. Results: Subcutaneous adipose tissue transcript levels and hepatic activity of 11βHSD1 were higher in postmenopausal vs. premenopausal women. In rodents, estrogen treatment to ovariectomized rats decreased visceral adipose tissue 11βHSD1, resulting in a shift towards higher subcutaneous (vs. visceral) 11βHSD1 mRNA expression/activity. Increased adipose and hepatic 11βHSD1 were associated with increased blood pressure and a disadvantageous blood lipid profile in humans. We found significant positive associations between 11βHSD1 and ERβ transcript levels in adipose tissue. The in vitro experiments showed upregulation of 11βHSD1 mRNA expression and activity with estrogen or ERβ-agonist treatment at low (corresponding to physiological) concentrations. Conclusions: Our studies show for the first time increased local tissue glucocorticoid activation with menopause/age in women. This may contribute to an increased risk of CVD. Estrogen treatment in rodents induces a shift in 11βHSD1 activity towards the subcutaneous adipose tissue depots, which may direct fat accumulation to this metabolically “safer” depot. The in vitro studies suggest that low-dose estrogen treatment upregulates 11βHSD1 via ERβ. In summary, estrogen - glucocorticoid metabolism interactions may be key in the development of menopause-related metabolic dysfunction and in part mediate the beneficial effects of postmenopausal estrogen treatment on body fat distribution.
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Ljunggren, Ribom Eva. "Muscles, Estrogen, and Bone." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3779.
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Silva, Teresa Cristina Barbosa Ferreira da. "Influência da obesidade e da doença arterial coronária nos níveis séricos de estrona nas mulheres na pós-menopausa." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-19042007-161309/.
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INTRODUÇÃO: Estudos recentes mostraram maior mortalidade em indivíduos nos extremos dos valores do índice de massa corpórea (IMC). Discute-se, também, a intensidade da influência da obesidade na mortalidade por doenças cardiovasculares (DCV), em mulheres na pós-menopausa, e da participação dos estrógenos endógenos. Neste trabalho, analisamos, prospectivamente, a influência da obesidade e os níveis séricos de estrona nos principais fatores de risco em mulheres na pós-menopausa com doença arterial coronária (DAC), ou de alto risco para DAC, matriculadas no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Estudo prospectivo, realizado entre março de 2004 e setembro de 2006, em 251 mulheres na pós-menopausa com alto risco para eventos cardiovasculares, na ausência de reposição hormonal. Foram estudadas, em 3 visitas semestrais (V1-basal, V2 e V3), as características clínicas (pressão arterial, índice de massa corpórea, fatores de risco para DCV, medicação utilizada, e ocorrência de eventos neste período) e as laboratoriais [glicemia, perfil lipídico, inflamatórias (análise PCR ultra-sensível), bem como e os níveis de estrógeno endógeno (estrona)]. Foram classificadas, segundo o IMC (kg/m2), em normal (18,5<=IMC<25), sobrepeso (25<=IMC<30) e obesa (>=30), e também os níveis de estrona (= e =pg/mL). Foram realizadas as análises univariada, curvas de Kaplan-Meier para mortalidade, segundo os níveis de estrona, e regressão multivariada de Cox. RESULTADOS: Não houve diferenças entre os grupos com relação à idade (71±8 vs 70±7 vs 69±6 anos; p=0,112). O aumento do IMC associou-se a maior prevalência de hipertensão arterial sistêmica (HAS) (81% vs 96% vs 100%; p<0,01), diabetes melito (38% vs 52% vs 69%; p=0,001), e níveis de estrona (22,3±11 vs 22,4±9,4 vs 28,2±16,4 pg/mL; p=0,002). Menores níveis de HDL (58±15 vs 53±12 vs 50±11 mg/dl; p=0,009) e LDL (123±30 vs 115±38 vs 107±36 mg/dl; p=0,039). Os níveis de PCR permaneceram inalterados (0,38±0,33 vs 0,79±1,81 vs 0,63±0,57 mg/dl; p=0,180) e houve tendência de maiores níveis de triglicérides (143±81 vs 167±80 vs 191±149 mg/dl; p=0,061). Níveis séricos de estrona >=25 pg/mL foram observados nas pacientes com maiores níveis de pressão arterial sistólica (140±18 vs 145±18 mmHg; p=0,031), pressão arterial diastólica (82±10 vs 85±9 mmHg; p=0,003), e maiores níveis de glicemia (123±48 vs 146±67 mg/dl; p=0,003), com menor prevalência de DAC (81% vs 67%; p=0,010). Para o seguimento de 1,99±0,54 anos, observou-se aumento gradativo dos níveis de estrona (V1=25±13, V2=31±14, V3=33±17 pg/mL; p<0,01). A incidência de eventos cardiovasculares, segundo os níveis de estrona =25 pg/mL, foi semelhante nos dois grupos analisados, e aconteceram no tempo médio de seguimento de 0,62±0,46 anos. Ocorreram 14 óbitos, sendo 8 por DCV, e 6 por outras causas. A curva de Kaplan-Meier mostrou uma tendência (p=0,074) de maior mortalidade, conforme os níveis de estrona =pg/mL. A idade [OR=1,08 (IC95%:1,01-1,18); p=0,037], PCR [OR=1,24 (IC95%:1,03-1,50); p=0,024] e HAS [6,22 (IC95%:1,86-20,81); p=0,003] foram as variáveis independentes para mortalidade. Conclusões: Nível sérico de estrona, para valor >=25 pg/mL, associou-se a menor prevalência de DAC, porém, não influenciou na incidência de eventos cardiovasculares, nem na mortalidade. Observou-se uma tendência de maior mortalidade em mulheres com níveis de estrona <=15 pg/mL. Na divisão em normal, sobrepeso e obesa observamos padrão de síndrome metabólica nas pacientes.INTRODUCTION: Recent studies showed higher mortality in people with extreme values of body mass index (BMI). The obesity\'s influence intensity in mortality associated with cardiovascular diseases (CVD) in postmenopausal women and the participation of the endogenous estrogens are unknown. In this study we analysed the influence of BMI and blood levels of estrone in the main risk factors for postmenopausal women (registered on the Heart Institute, University of São Paulo Medical School) with coronary artery disease (CAD) or with high risk for CVD. METHODS: Prospective study performed between March/2004 and September/2006, in 251 postmenopausal women with high risk for cardiovascular events in the absence of hormonal therapy. They were studied, in 3 biannual visits (V1-baseline, V2 and V3), clinical characteristics (blood pressure, BMI, risk factors for CVD, medication in use and events occurred during this period), laboratories exams [glucose, total cholesterol, HDL-cholesterol, LDL- cholesterol, triglyceride, C-reactive protein and blood levels of endogenous estrogen (estrone)]. They were classified according to the BMI (kg/m2) in normal (18,5<=IMC<25), overweight (25<=IMC<30) and obese (>=30) and blood levels of estrone (= and =pg/mL). Univariate analysis, Kaplan-Meier estimation curves according to the blood levels of estrone and the Cox multivariate regression were done. RESULTS: No differences were seen among the groups regarding age (71±8 vs 70±7 vs 69±6 years; p=0,112). The increase of BMI was associated with higher prevalence of hypertension (81% vs 96% vs 100%; p<0,01), diabetes melito (38% vs 52% vs 69%; p=0,001) and blood levels of estrone (22,3±11 vs 22,4±9,4 vs 28,2±16,4 pg/mL; p=0,002); lower levels of HDL-cholesterol blood (58±15 vs 53±12 vs 50±11 mg/dL; p=0,009) and LDL-cholesterol (123±30 vs 115±38 vs 107±36 mg/dL; p=0,039). The levels of C-reactive protein remained unchanged (0,38±0,33 vs 0,79±1,81 vs 0,63±0,57 mg/dL; p=0,180) and a trend of higher levels of triglycerides (143±81 vs 167±80 vs 191±149 mg/dL; p=0,061). Blood level of estrone >=25 pg/mL was observed in pacientes with higher level of systolic blood pressure (SBP) (140±18 vs 145±18 mmHg; p=0,031), diastolic blood pressure (DBP)(82±10 vs 85±9 mmHg; p=0,003) and higher levels of glucose (123±48 vs 146±67 mg/dL; p=0,003), with lower prevalence of CHD (81% vs 67%; p=0,010). During the follow-up of 1,99±0,54 years was noticed a gradual increase of blood level of estrone (V1=25±13, V2=31±14, V3=33±17 pg/mL; p<0,01). The incidence of cardiovascular events according to the blood levels of estrone =25 pg/mL was similar in the two groups and occurred during the follow-up period of 0,62±0,46 years. Were reported 14 deaths: 8 associated with CVD and 6 related to another causes. The Kaplan-Meier estimation curve showed a trend (p=0,074) of greater mortality for CVD according the blood level of estrone of =15 pg/mL. The age [OR=1,08 (IC95%:1,01-1,18);p=0,037], C-reactive protein [OR=1,24 (IC95%:1,03-1,50);p=0,024] and hypertension [6,22 (IC95%:1,86- 20,81);p=0,003] were independent variables for mortality. CONCLUSIONS: Blood level of estrone for readings of >=25 pg/mL, can be associated with smaller prevalence of CAD, but had no impact in cardiovascular events and mortality. We noticed a trend of greater mortality in women with estrone level lower than 15 pg/mL.
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James, Karen Elizabeth. "Synthesis and biochemical evaluation of inhibitors of estrone sulfatase." Thesis, Kingston University, 2000. http://eprints.kingston.ac.uk/20650/.
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The use of enzyme inhibitors in the treatment of patents with hormone-dependant breast cancer is discussed. Particular emphasis is placed on the inhibition of the enzymes 17[beta]-hydroxysteroid dehydrogenase, aromatase, and estrone sulfatase. Novel inhibitors of estrone sulfatase have been designed, synthesised, and subsequently subjected to biochemical testing to assess their inhibitory activity. From this study a number of highly potent non-steroidal compounds have been identified which appear to be the most potent non-steroidal estrone sulfatase inhibitors known to date. Investigation into the structural activity relationships that exist within the sulfamate-containing inhibitors has been undertaken, and a correlation has been identified between the p[kappa][sub]a of the parent phenol compound and the potency of the sulfamate derivative against estrone sulfatase. Finally, the design, synthesis, and biochemical evaluation of dual inhibitors of estrone sulfatase and aromatase has begun. These studies have helped to identify potential new lead compounds in the treatment of hormone dependent breast cancer.
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Groth, Milena Barbara. "Photodegradation of estrone in aqueous matrix, followed by HPLC." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/13550.
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Mestrado em Química - Química Analítica e QualidadeEndocrine disrupting chemicals (EDCs) are compounds with detrimental effects on the endocrine activity of the natural hormones in the human and animals. Besides industrial chemicals, some estrogens (both natural and synthetic) are found to be the most potent EDCs. Photodegradation is an important pathway for removing of estrogens from the aquatic system. Estrone (E1) is one of the steroidal estrogens existing widely in the aquatic environment and was found to be the most abundant estrogen in aquatic systems. The main goal of this work was to investigate the photodegradation of E1 in water under simulated solar radiation and to estimate the impact of different fractions of HSs (HA, FA and XAD-4). So far not many studies conducted on the impact of OM, existing in natural water on the photodegradation of E1. Therefore, the same experiment were done in the natural water with different content of OM, depending on the origin. The testing of E1 photodegradation with addition of singlet oxygen scavenger have been also performed. The results indicated that E1 was photodegraded even in the absence of OM with a half-life of 6 h. The presence of HSs enhanced the photodegradation in presence of all HS fractions accelerating the photodegradation of E1 with increasing concentrations of HSs. The effect of structural differences between HA, FA and XAD-4 on photodegradation of E1 has been studied. Experiments performed in natural water have shown the impact of origin of water samples on the rate of E1 photodegradation, which is related to different content of OM and salinity. The results of studies have shown inhibitory effect of the presence of sodium azide, as a singlet oxygen scavenger, on the photodegradation of E1. The presence of both OM and scavenger, have proven to reduce the photodegradation in both wastewater samples, but the effect was more pronounced in the case of sample after primary treatment (STPP). The LOD of 17.4 μg/L was achieved with HPLC-FLD procedure for the analysis of E1 in aqueous samples.
A importante colaboração de diversas personalidades ligadas à área da Desreguladores endócrinos (EDC) são compostos com efeitos negativos sobre a atividade endócrina das hormonas naturais em animais e humanos. Além dos produtos químicos industriais, alguns estrogénios (naturais e sintéticas) são considerados os EDCs mais potentes. A fotodegradação é uma importante via de remoção dos estrogénios do sistema aquático. A estrona (E1) é uma das hormonas esteróides mais abundante nos sistemas aquáticos. Neste trabalho investigou-se a degradação de E1, sob radiação solar simulada, e a influência da presença de diferentes frações de HSs (HA, FA e XAD-4) de origem aquática no processo de fotodegradação. Foram ainda testadas águas naturais com diferentes teores de matéria orgânica (OM). Pesquisou-se, ainda a formação de oxigénio singuleto nas amostras irradiadas utilizando um sequestrador do mesmo.. Os resultados indicaram que E1 foi fotodegradado mesmo na ausência de OM com uma semi-vida de 6 h. A presença de HSs reforça a fotodegradação de E1 na presença de todas as fracções de HS a qual sofre aceleração com o aumento das suas concentrações. Foi investigada a influência das diferenças estruturais dos HA, FA e XAD-4 sobre a fotodegradação de E1. As experiências realizadas em águas naturais demonstraram o impacto da origem das amostras sobre a taxa de fotodegradação E1, a qual está relacionada com conteúdo de OM e com a salinidade. Para testar a formação de oxigénio singuleto durante a irradiação da matéria orgânica das águas naturais na presença de E1, foi utilizada a azida de sódio, como sequestrador de oxigénio singuleto. A presença de OM e azida de sódio, provaram reduzir a fotodegradação em ambas as amostras de águas residuais, mas o efeito foi mais pronunciado no caso da amostra de uma ETAR depois do tratamento primário (STPP). Assim, ficou provada a formação de oxigénio singuleto, quando se irradia a matéria orgânica, o qual intervem no processo de fotodegradação de E1. As análises químicas de E1 foram feitas por HPLC-FLD tendo-se obtido um LOD de 17,4 μg/L.
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Curran, Edward M. "Regulation of the estrogen receptor in human breast cancer cells /." free to MU campus, to others for purchase, 1998. http://wwwlib.umi.com/cr/mo/fullcit?p9901231.
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Karolczak, Magdalena [Verfasser]. "Estrogen synthesis and novel mechanisms of estrogen action in the developing brain / Magdalena Karolczak." Ulm : Universität Ulm. Medizinische Fakultät, 2001. http://d-nb.info/1015473156/34.
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Knauer, Mark. "Genetics of gilt estrous behavior." NCSU, 2009. http://www.lib.ncsu.edu/theses/available/etd-10302009-095808/.
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Studies were conducted to develop and analyze gilt estrous behavior traits. Variance components, genetic correlations, and genetic line differences were estimated for gilt estrus, puberty, growth, composition, structural conformation, and first litter sow reproductive measures. Four groups of Landrace-Large White gilts (n=1,225, GIS of NC) from 59 sires and 330 dams were utilized. Heritability (h2) estimates for estrous traits; estrus length, maximum strength of standing reflex with a boar, total strength of standing reflex with a boar, maximum strength of standing reflex without a boar, total strength of standing reflex without a boar, vulva redness, strength of vulva reddening and swelling (VISUAL VULVA), and vulva width were 0.21, 0.13, 0.26, 0.42, 0.42, 0.26, 0.45, and 0.58, respectively. For puberty traits; age at puberty, puberty weight, puberty backfat, and puberty longissimus muscle, h2 estimates were 0.29, 0.39, 0.41, and 0.38, respectfully. The h2 of whether or not a gilt farrowed a litter (STAY1) was 0.14. Age at puberty had favorable genetic associations with estrus length, maximum strength of standing reflex with a boar, vulva redness, STAY1, and age at first farrowing (AFF) (-0.23, -0.32, 0.20, -0.27, and 0.76, respectively). Genetic correlations between estrus length and the standing reflex traits with STAY1 (0.34 to 0.74) and AFF (-0.04 to -0.41) were positive and negative, respectively. Growth rate had unfavorable genetic correlations with estrus length, the standing reflex traits, vulva redness, STAY1, and AFF (0.30, 0.14 to 0.34, -0.19, 0.52, and -0.25, respectfully). Backfat had unfavorable genetic associations with estrus length, age at puberty, and first litter total number born (TNB1) (0.29, -0.26, and 0.47, respectively). Vulva redness and TNB1 had favorable phenotypic and genetic correlations (-0.14 and -0.53, respectively). For estrous traits, crossbred performance was superior to the pure-line average for estrus length, total strength of standing reflex with a boar, vulva redness, VISUAL VULVA, and vulva width. These findings imply the use of F1 females would increase estrus length and improve vulva traits. The unfavorable genetic associations between production and reproduction traits further strengthen the need for a balanced selection objective. Based on these results it was concluded that selection for a younger age at puberty would have correlated responses of improved gilt estrous behavior and sow reproductive lifetime.
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Islander, Ulrika. "Immunomodulation by estrogen and estren /." Göteborg : Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at Göteborg University, 2007. http://hdl.handle.net/2077/3123.
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Wade, Christian Bernard. "Mechanisms of estrogen rapid signaling /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/6272.
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Wen, Huajing. "Removal of estrone from water with adsorption and UV Photolysis." Digital WPI, 2006. https://digitalcommons.wpi.edu/etd-theses/704.
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This work investigated the combined technology of adsorption on hydrophobic molecular sieves (zeolites) and direct UV (254 nm) photolysis for removing estrone (E1) from water. The target compound estrone belongs to the group of endocrine-disruptor compounds (EDCs) that are raising more and more concern due to increasing evidence of their adverse estrogenic effects on aquatic organisms and humans. Current wastewater treatment processes remove less than 80% of estrone on average. However, because of its strong biological potency, small amounts are still able to exert adverse estrogenic effects on aquatic systems. Consequently, advanced treatment technologies have been investigated in the hope of reaching higher removal efficiency. Adsorption of estrogens on hydrophobic zeolites in this work is a potential new alternative. Based on the hydrophobic nature of estrogens including E1, two types of zeolites, dealuminated Y (DAY) and silicalite-1, and a type of granular activated carbon Centaur® activated carbon (GAC) were evaluated for adsorption capacity. The results demonstrated that DAY is the best adsorbent for E1 in that 99% E1 can be removed by DAY. Silicalite-1 was the least effective. Moreover, adsorption of E1 to DAY is much faster. Estrone reached adsorption equilibrium in 4 hours on DAY versus 8 days for GAC. The adsorption data of DAY for E1 were fit to the Freundlich and Langmuir equations and the maximum adsorption capacity is estimated as 74 mg E1/g DAY. Direct UV photolysis of E1 in solution was also evaluated. Short-wave UV (ë = 254 nm) degraded E1 in solution much more effectively than long-wave UV-light (ë = 365 nm). No significant increase in degradation of E1 in UV photolysis was found with the addition of hydrogen peroxide. The regeneration of E1-contaminated DAY was investigated by a series of adsorption/direct UV (ë = 254nm) irradiation cycles. No significant deterioration of adsorption capacity of DAY was observed over nine adsorption/regeneration cycles.
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Zushin, Peter-James H. "The selective effect of estrogen receptor alpha and beta on activity and social behavior in neonatal male praire voles." Akron, OH : University of Akron, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=akron1248102221.
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Thesis (M.S.)--University of Akron, Dept. of Biology, 2009."August, 2009." Title from electronic thesis title page (viewed 10/7/2009) Advisor, Bruce Cushing; Committee members, Qin Liu, Todd Blackledge; Department Chair, Monte Turner; Dean of the College, Chand Midha; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.
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Nascimento, Ezequiel Batista do. "Efeitos de diferentes tipos estressores sobre a mem?ria e aprendizagem de ratas." Universidade Federal do Rio Grande do Norte, 2013. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17355.
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The exposure to stressors produces physiological changes of the organism in order to adapt the individual to the environment. Depending on the type, intensity and duration, stress can affect some cognitive functions, particularly processes of learning and memory. Several studies have also proposed that some level of anxiety would be necessary for memory formation. In this context, memories of previously aversive experiences may determine the manner and intensity with which are expressed fear responses, which explains the great interest in analyzing both anxiety and memory in animals. In addition, males and females demonstrate different reactions in relation to stressful stimuli, showing different levels of anxiety and differences in processing of the acquisition, retention and recall of information. Based on this information, the present study aimed to verify the effect of stress on learning, memory and anxiety behavioral parameters in rats exposed at different types of stressors of long duration (seven consecutive days): restraint (4h/day), overcrowding (18h/day) and social isolation (18h/day) in the different phases of the estrous cycle. Our results showed that the stress induced by restraint and social isolation did not cause changes in the acquisition process, but impaired the recall of memory in rats. Furthermore, it is suggested a protective effect of sex hormones on retrieval of aversive memory, since female rats in proestrus or estrus phase, characterized by high estrogen concentrations, showed no aversive memory deficits. Furthermore, despite the increased plasma levels of corticosterone observed in female rats subjected to restraint stress and social isolation, anxiety levels were unaltered, compared to those various stress conditions. Animal models based on psychological and social stress have been extensively discussed in the literature. Correlate behavioral responses, physiological and psychological have contributed in increasing the understanding of stress-induced psychophysiological disorders
A exposi??o a fatores estressantes promove mudan?as fisiol?gicas adaptativas do organismo ao meio ambiente. Dependendo do tipo, da intensidade e dura??o, o estresse pode afetar algumas fun??es cognitivas, particularmente o processo de aprendizagem e de mem?ria. Alguns estudos tamb?m t?m proposto que a ansiedade, em certa medida, seria necess?ria para que ocorresse a forma??o da mem?ria. Neste contexto, mem?rias de experi?ncias aversivas anteriores podem determinar a maneira e a intensidade com que s?o expressas as respostas de medo, o que justifica o grande interesse em analisar simultaneamente ansiedade e mem?ria em animais. No mais, machos e f?meas apresentam rea??es distintas em rela??o a est?mulos estressores, mostrando diferentes n?veis de ansiedade e diferen?as no processamento da aquisi??o, reten??o e evoca??o de informa??es mnem?nicas. Frente a essas informa??es, o presente estudo teve como objetivo verificar o efeito do estresse em par?metros comportamentais de aprendizagem, mem?ria e ansiedade de ratas submetidas a diferentes tipos de estressores de longa dura??o, (sete dias consecutivos): conten??o (4h/dia), alta densidade populacional (18h/dia) e isolamento social (18h/dia), nas diferentes fases do ciclo estral. Nossos resultados mostraram que o estresse promovido pela conten??o e pelo isolamento social n?o promoveram altera??es no processo de aquisi??o, mas promoveu preju?zos na evoca??o da mem?ria de ratas. Al?m disso, sugere-se um efeito protetor dos horm?nios sexuais sobre a evoca??o da mem?ria aversiva, uma vez que ratas que estavam nas fases proestro ou estro, fase de altas concentra??es plasm?ticas de estr?genos, n?o apresentaram preju?zos na evoca??o dessa mem?ria. No mais, apesar do aumento dos n?veis plasm?ticos de corticosterona observado nas ratas submetidas ao estresse de conten??o e isolamento social, os n?veis de ansiedade permaneceram inalterados frente a essas diferentes condi??es de estresse. Modelos animais baseados em estresse psicol?gico e social t?m sido bastante abordados na literatura. Correlacionar respostas comportamentais, fisiol?gicas e psicol?gicas t?m contribu?do no aumento da compreens?o dos transtornos psicofisiol?gicos envolvidos na resposta de estresse
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Russell, Nancy. "Estrogen Receptor Alpha in the Medial Preopic Area Mediates Male Rat Sexual Responses to Estrogen." Digital Archive @ GSU, 2010. http://digitalarchive.gsu.edu/biology_theses/25.
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Male rat sexual behavior requires aromatization of testosterone (T) to estradiol (E2) in the medial preoptic area (MPO) where estrogen receptors (ER) exist in two isoforms, ERα and ERβ. We hypothesized that E2 acts through estrogen receptor α (ERα) in the MPO to promote male mating behavior. Four groups of male rats were castrated, administered DHT s.c. and bilateral MPO implants delivering either: cholesterol, E2, propyl pyrazole triol (PPT, ERα agonist), diarylpropionitrile (DPN, ER β agonist), or 1-methyl-4-phenyl pyridinium (MPP, ERα antagonist). Additional gonadally intact males received bilateral MPO DPN implants. PPT maintained sexual behavior equally as well as E2, whereas mating was not maintained by cholesterol or DPN MPO implants. Exogenous T did not reinstate mating in animals that received MPP MPO implants. These findings indicate that, in the MPO, ERα is necessary and sufficient to promote copulatory behavior in male rats and ERβ is not sufficient for mating.
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Couse, John Floyd. "THE ROLE OF ESTROGEN RECEPTOR-a AND ESTROGEN RECEPTOR-b IN THE HYPERLUTEINIZED MOUSE OVARY." NCSU, 2004. http://www.lib.ncsu.edu/theses/available/etd-05212004-123339/.
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The hypothalamic-pituitary-gonadal (HPG) axis was characterized in female mice lacking one or both forms of estrogen receptor (ERa, ERb) with the aim of elucidating the contribution of each receptor form to gonadotropin homeostasis and ovarian function. These studies consisted of a thorough evaluation of gene expression for the gonadotropin subunits in the pituitary and the components necessary for steroidogenesis in the ovary. These data were corroborated with evaluations of the plasma levels for each of the relevant pituitary and gonadal hormones. Females lacking ERb (bERKO) exhibit minimal disruption in HPG axis function but do exhibit deficits in gonadotropin responsiveness in the ovary. Females lacking ERa (aERKO) exhibit dramatic ovarian phenotypes of hemorrhagic and cystic follicles and exaggerated steroid synthesis in the ovaries. The phenotypes in the aERKO ovary are attributable to chronically elevated LH due to the loss of ERa function in the hypothalamus. Pharmacologic reduction of plasma LH levels in aERKO females abates the ovarian phenotypes. These studies indicate that the hypothalamic functions of ERa are most critical to ovarian function. To better understand the contribution of ERb to the manifestations of LH-hyperstimulation in the ovary, females lacking functional ERb but possessing elevated LH via a transgene (bERKOLHCTP) were generated. Characterization of bERKOLHCTP animals indicates the intraovarian functions of ERb are necessary for the induction of LH-associated cystic follicles but not amplified steroidogenesis. An additional novel finding in aERKO ovaries was ectopic expression of the Leydig cell specific enzyme, 17b-HSD III and correlating male-like testosterone synthesis. This phenotype is dependent on LH-hyperstimulation of ovaries lacking ERa function to manifest. In summary, the predominant contribution of ERa to ovarian function occurs in the hypothalamus, whereas ERb is more important within the ovary itself. Presence of Leydig cell specific gene expression in aERKO ovaries indicates a potential role for estradiol and ERa in gonadal differentiation.
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Shen, Minqian. "Roles of estrogen hormones and estrogen receptors on regulation of liver and liver cancer metabolism." Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1492612390075921.
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Hopkins, Katherine Lee. "In vitro characterization of aromatase, estrone sulfotransferase and estrone sulfatase activities in the porcine placenta and endometrium at 30, 60 and 90 days of gestation." Thesis, Virginia Tech, 1987. http://hdl.handle.net/10919/45793.
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The purpose of this investigation was to characterize the activities of three enzymes, aromatase, estrone (E1) sulfotransferase and E] sulfatase, in the porcine placenta and endometrium on d 30, 60 and 90 of gestation. These enzymes play key roles in determining in utero concentrations of estrogens. Days 30, 60 and 90 were chosen because previous investigations had determined that these were times of substantial changes in in vitro estrogen production by the porcine placenta and endometrium.
Master of Science
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Giton, Frank Fiet Jean Chopin Dominique. "Rôle émergent des oestrogènes dans le cancer de la prostate." Créteil : Université de Paris-Val-de-Marne, 2008. http://doxa.scd.univ-paris12.fr:80/theses/th0406109.htm.
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Björnström, Linda. "Molecular mechanisms of alternative estrogen receptor signaling /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-509-3/.
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Ansell, Peter James. "Regulation of the antioxidant response element by estrogens : a potential mechanism to help explain estrogen-induced cancer? /." free to MU campus, to others for purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p3137674.
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Ullman, Jeffrey Layton. "The chemical behavior of estrone and 17beta-estradiol in the environment." Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/5924.
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The endogenous hormones estrone and 17ò-estradiol support vertebrate growth and development, but slight increases above ambient concentrations may paradoxically induce endocrine disruption, leading to increased frequencies of reproductive disorders and cancer in humans and wildlife. Livestock excrete estrogenic compounds which can lead to surface and groundwater contamination. Limited information exists concerning estrogen fate and transport, as exposure concerns have recently arisen. This study examined the chemical behavior of estrone and 17ò-estradiol with the goal of elucidating manure management principles applicable to animal feeding operations (AFOs). Both compounds indicated that they are susceptible to physicochemical and biological decomposition. Photolysis yielded 27- and 35-day half-lives for estrone and 17ò-estradiol at pH 7, respectively, based on test conditions. 17ò-estradiol photolysis exhibited a slight pH-dependent behavior. Mineralization produced half-lives ranging from 7 to 15 days for estrone and 3 to 7 days for 17ò-estradiol. Indigenous microbial populations did not demonstrate a lag phase and therefore appeared to have been well acclimated to degrading these compounds. Anaerobic lagoon supplements did not affect mineralization rates. The compounds had partition coefficients ranging from 2 to 4.4 mL g-1, depending on soil characteristics. Estrone and 17ò-estradiol had a higher absorptivity to soils with greater clay content and organic matter. Once sorbed, binding appeared largely irreversible with minimal desorption. Column experiments detected no estrone in the leachate for the finer textured soils, while estrone had completely migrated through the loamy fine sand after 7 pore volumes. Hypothetical scenarios, simulated using HYDRUS-1D, evaluated the combined effects of soil texture and the values obtained for sorption and mineralization on leaching. Model results indicated rapid leaching in loamy sand, while sandy clay loam and clay yielded significantly slower estrone and 17ò-estradiol movement with concentrations 1 to 3 orders of magnitude lower. Data suggest that estrogens applied to sandy soil may leach and contaminate groundwater, especially in the presence of shallow water tables. Sandy clay loam and clay likely present minimal risk for subsurface mobility, but simulated accumulation near the soil surface may promote transport via overland flow. Sound manure management practices will likely reduce off-site transport of estrogens originating from AFOs.
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Rafi, Ali. "Estrogen action in growth plate cartilage." Thesis, Högskolan i Skövde, Institutionen för vård och natur, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-5463.
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Park, Se Hyung. "Estrogen in ovarian cancer cell metastasis." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/1287.
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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.
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Eng, Frank Chung Sing 1972. "Molecular mechanisms of estrogen receptor signaling." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38483.
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The estrogen receptor (ER) is a ligand dependent transcriptional activator that belongs to the steroid/nuclear receptor superfamily. To probe the structure and function of the ER ligand binding domain (LBD), we developed a genetic screen in yeast Saccharomyces cerevisiae using a library of reverse ERs screened with a low affinity estrogen agonist, 2-methoxyestrone. Mutants isolated from this screen demonstrated altered ligand binding and/or transactivation properties. One of these mutants, L536P, showed high levels of constitutive activity in several transiently transfected cells and a HeLa line that stably propagates an estrogen-sensitive reporter gene. This suggests that substitution of a proline at position 536 in the wild type ER (HEGO) induces a reversible conformational change in the region of AF-2 that partially mimics activation of the receptor by hormone binding.Activation of transcription by the ER requires the recruitment of different classes of coactivators. L536P interacted with coactivators in the absence of hormone and this constitutive interaction can be abolished by antiestrogens. We conclude that constitutive activity of L536P-HEGO is manifested to in part from constitutive coactivator binding. We also demonstrated that different classes of coactivators do not recognize the ER LBD in the same manner and can compete for binding to the ER LBD suggesting that different classes of coactivators recognize distinct but overlapping binding sites. Interestingly, coexpression of RIP140 blocked enhanced transactivation by HEGO observed in the presence of TIF-2, suggesting that RIP140 may play a negative role in ER signaling.
Using a yeast two-hybrid system with the ER LBD as bait, we isolated a novel estrogen receptor cofactor (ERC) that interacts with the ER LBD in a hormone dependent manner. The primary structure of ERC consists of 4 ankyrin repeat domains, 2 LXXLL motifs and an ATP/GTP binding domain. ERC is highly expressed in ovary, testes, and spleen, with moderate levels in heart, brain, and placenta. ERC repressed ER transactivation in several cell lines in the presence of estradiol suggesting that ERC may function as a novel estrogen dependent repressor of the ER. Immunohistochemistry and confocal microscopy localized ERC to the cytoplasm with partial nuclear staining. Recently, synphilin-1, a novel protein that has been implicated in the pathogenesis of Parkinson's disease was isolated and is identical to ERC. A role for ERC in intracellular signaling through a membrane bound ER in the brain is currently being investigated.
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Greiwe, Kelly. "Effects of estrogen on aggressive behavior." Connect to resource, 2006. http://hdl.handle.net/1811/6576.
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Thesis (Honors)--Ohio State University, 2006.Title from first page of PDF file. Document formatted into pages: contains 18 p.; also includes graphics. Includes bibliographical references (p. 16-18) Available online via Ohio State University's Knowledge Bank.
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Mhyre, Andrew James. "Mechanisms of estrogen signaling in astrocytes /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/6266.
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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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Singer, Cherie A. "Neurotrophic and neuroprotective effects of estrogen /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/6301.
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Jain, Disha. "New approaches to estrogen receptor modulation." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 157 p, 2009. http://proquest.umi.com/pqdweb?did=1818417411&sid=4&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Nelson, Adam William. "Estrogen receptor beta modulates prostate carcinogenesis." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267736.
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Prostate cancer (PC) is characterised by dependence upon androgen receptor (AR) as its driving oncogene. When organ-confined, radical treatment can be curative, however there is no cure for advanced, castration-resistant prostate cancer (CRPC). There is therefore a need to better understand the biology of PC, and how influencing AR can modify disease progression. Estrogen is essential for prostate carcinogenesis with evidence from epidemiological, in vitro, human tissue and animal studies. Most suggests that estrogen receptor beta (ERβ) is tumour-suppressive, but trials of ERβ-selective agents have not improved clinical outcomes. ERβ has also been implicated as an oncogene, therefore its role remains unclear. Additional evidence suggests interplay between ERβ and AR, the mechanisms of which are uncertain. The study hypothesis ‘ERβ is an important modulator of prostate carcinogenesis’ was developed to establish whether targeting ERβ could affect PC progression. Much of the confusion around ERβ stems from use of inadequately validated antibodies and cell line models. The first phase of this work was to test ERβ antibodies using an ERβ-inducible cell system. Eight ERβ antibodies were assessed by multiple techniques, showing that commonly used antibodies are either non-specific or only specific in one modality. Two reliable antibodies were identified. Next, cell lines previously used to study ERβ were assessed using validated antibodies and independent approaches. No ERβ expression was detected; an important finding that casts doubt on previously published ERβ biology. Subsequently, a PC cell line with inducible ERβ expression (LNCaP-ERβ) was developed and validated to enable controlled experiments on the effects of ERβ on proliferation, gene expression and ERβ/AR genomic cross-talk. Phase three of this work focused on ERβ biology in PC and its relationship to AR. Interrogation of clinical datasets showed that greater ERβ expression associated with favourable prognosis. Gene expression data from men treated with androgen deprivation therapy revealed that AR represses ERβ. This was confirmed in vitro. The LNCaP-ERβ cell line was treated with androgen and/or ERβ-selective estrogen. Activated ERβ in the presence of androgen-stimulated AR inhibited cell proliferation and down-regulated androgen-dependent genes. Genome-wide mapping of ERβ binding sites reveals that ERβ antagonises AR through competition for shared DNA binding sites. In conclusion, ERβ expression is down-regulated by AR during malignant transformation of prostate epithelium. We reveal an antagonistic relationship between ERβ and AR whereby sustaining or replacing ERβ may inhibit tumour growth through down-regulation of AR-target genes. In future, an ERβ-selective compound may be used to slow or abrogate PC progression.
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Mobley, James Austin. "Oxidative mechanisms of estrogen induced carcinogenesis /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu148819623490807.
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Zilmer, Johansen Anne Katrine. "Estrogen metabolism in pulmonary arterial hypertension." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5199/.
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Pulmonary arterial hypertension (PAH) is a devastating and progressive vasculopathy of the pulmonary arteries for which there is no cure. There is an urgent need for more effective therapies. PAH is characterised by elevated pulmonary arterial pressures and obstructive vascular lesions in the distal vasculature by excessive cellular proliferation. As a result, the right ventricle is placed under excessive strain resulting in adaptive hypertrophy which progresses to maladaptive hypertrophy and failure. PAH is more common in women than in men suggesting that estrogens may be integral to disease pathogenesis. Understanding the biological basis for this sex difference would offer a new treatment paradigm in this devastating cardiovascular disease. Here, we challenged the concept that the estrogen metabolic axis is dysregulated in PAH New insights have revealed a potential contribution of the estrogen metabolizing enzyme, cytochrome P450 1B1 (CYP1B1) in the development of PAH. 17β-estradiol (17β-E2) and estrone (E1) are metabolized by the activity of CYP1B1 to the 2-, 4- and 16-hydroxylated estrogens. Here, we defined the role of CYP1B1 in the pathogenesis of PAH. CYP1B1 expression was increased in both experimental (hypoxia and SU5416+hypoxia) and in heritable and idiopathic PAH (HPAH and IPAH, respectively). Both male and female CYP1B1 knockout mice (CYP1B1-/-) were challenged with chronic hypoxia to induce PAH as assessed by right ventricular systolic pressures (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodeling. CYP1B1-/- mice were protected against hypoxia-induced pulmonary hypertension (PH). CYP1B1 inhibition with the highly potent and selective inhibitor 2,3',4,5'-tetramethoxystilbene (TMS; 3 mg/kg/day by intra-peritoneal injection) attenuated the development of hypoxia-induced PH. Only moderate effects were observed with CYP1B1 inhibition in monocrotaline-induced PH, despite improving survival rates. Female mice that over-express the human serotonin transporter gene (SERT+ mice) develop a spontaneous PAH phenotype at 5 months of age which is dependent on circulating levels of 17β-E2. Here, we provide evidence that the estrogen metabolic axis is dysregulated in these mice and this may underlie their PAH phenotype. The estrogen synthesizing enzyme aromatase and CYP1B1 was increased in whole lung homogenates of female SERT+ mice compared to wild-type mice. Despite increased expression of aromatase, 17β-E2 concentrations were unchanged. CYP1B1 inhibition with TMS (1.5mg/kg/day by intra-peritoneal injection) attenuated the PAH phenotype in female SERT+ mice as assessed by RVSP and pulmonary vascular remodeling Other studies have identified that the 16-hydroxylated metabolites of estrogens (17β-E2 and E1) are the only CYP1B1 metabolites to induce cellular proliferation, with the most profound effects observed with 16α-hydroxyestrone (16α-OHE1). In mice exposed to chronic hypoxia, urinary concentrations of 16α-OHE1 were increased. Chronic dosing of 16α-OHE1 in mice (1.5mg/kg/day by intra-peritoneal injection for 28 days) resulted in the development of a PAH phenotype in female mice only. 16α-OHE1 induced cellular proliferation in human pulmonary arterial smooth muscle cells (hPASMCs) and this was inhibited by a scavenger of reactive oxygen species (ROS) and an inhibitor of extracellular regulated kinase 1/2 (ERK 1/2). 4-hydroxylation is the predominant metabolic pathway activated by CYP1B1 activity and we therefore investigated the effects of the 4-hydroxylated metabolite of 17β-E2 in vivo. 4-hydroxyestradiol (4-OHE2) had no effects on PAH parameters in mice (1.5mg/kg/day by intra-peritoneal injection for 28 days). However, serotonin-induced vasoconstriction of the intra-pulmonary arteries was dramatically reduced in arteries harvested from mice dosed with 4-OHE2. More recent studies have identified that 4-hydroxyestrone (4-OHE1) is the predominant CYP1B1 metabolite in the lungs of mice. Interestingly, despite evidence for a pathogenic function of CYP1B1 activity in vivo, 4-OHE1 inhibited cellular proliferation in hPASMCs as assessed by thymidine incorporation whilst no effects were reported on cell viability. We provide evidence for an altered estrogen metabolic axis in PAH, by in part, overexpression of the putatively pathological CYP1B1. Yet, the dynamic estrogen metabolic profile in pulmonary vascular cells remains undetermined. To address this, we developed a high fidelity HPLC method to quantitatively fate map estrogen metabolism in hPASMCs to determine the dynamic regulation of estrogen metabolism in PAH. We provide the first direct evidence that hPASMCs metabolize 17β-E2 and that estrogen metabolism is pathologically altered in PAH. Our metabolic screen revealed a prominent role for 17β-hydroxysteroid dehydrogenase enzymes in hPASMCs by rapid formation of E1 in all groups studied, increasing with time, with the highest activity in male control hPASMCs and the lowest activity in female control hPASMCs. In female control hPASMCs there was no evidence of CYP activity, whilst numerous metabolites were formed in the other groups studied. The formation of the pathogenic 16α-hydroxylated estrogens was only evident in PASMCs from both male and female PAH patients at 24 and 48 hours. Globally, this study introduces a platform to elucidate effects of PAH insults and potential therapies on the estrogen-metabolic profile in pulmonary vascular cells. Overall, we provide eminent evidence that the estrogen metabolic axis is pathologically altered in PAH and is influenced by gender. This provides a strong rationale for the application of estrogen-sensitive therapies in the management of this highly female discriminating disease.
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Oliveira, Thiago Sardinha de. "Efeito vasorelaxante da estrona sobre aorta torácica de ratos: contribuição ao estudo do mecanismo de ação." Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/4871.
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Endogenous estrogens have been associated with greater vascular protection in premenopausal women, and the increased risk of cardiovascular diseases in postmenopausal women can be associated to the decrease in plasma estrogen levels. Furthermore recently studies showed that the use of estrogens, like estrone, exhibits remarkable vascular effect when used on isolated arteries, however any investigation was made to elucidate the mechanism of action of this compound. So, the present study was designed to investigate the ability of estrone to induce vascular relaxation and modulate NO-dependent signaling pathway and analyzed the role of estrogens receptor on estrone-mediated vascular relaxation, compared with the effects promoted by 17β-estradiol. 12 week-old male Wistar rats were used to the vascular reactivity, which was performed in an organ bath study for an isometric tension recording. To the experimental protocols, concentration-response curves (0.1 - 100μM) to estrone or 17β - estradiol were performed. The mechanism contributing to estrone-induced effects were determined comparing with the vascular effects induced by 17β - estradiol that have its effect vascular well characterized. It was observed that the vascular relaxation promoted by estrone is dependent on the endothelium and the estrogen receptor. The vasorelaxant effect promoted by estrone was significantly altered in the presence of the inhibitor of PI3K signaling pathway (wortmannin) and the Ca2+-CaM complex inhibitor (calmidazolium), showing the involvement of PI3K/Ca2+-CaM signaling pathways. This study demonstrate that estrone promoted vasorelaxant effect on rat thoracic aortic on endotheliumdependent manner and its effect depends on the estrogen receptors that activate the PI3K pathway and the Ca2+-calmodulin complex which subsequently activates the NO/cGMP pathway. These results contribute to the better understanding of the role of estrone in the conjugated equine estrogen (CEE) which could be associated to the benefits effects of estrogens in the CEE therapy.
Os estrogênios endógenos têm sido associados com uma maior proteção do sistema vascular em mulheres na pré-menopausa, uma vez que os riscos de doenças cardiovasculares em mulheres na pós-menopausa são maiores, alterações estas que se devem à diminuição nos níveis plasmáticos de estrogênios. Além disso, estudos recentes mostraram que o uso de estrogênios, como a estrona, apresenta notável efeito vasorelaxante quando avaliado seu efeito em artérias isoladas, no entanto, nenhuma investigação foi realizada para elucidar o mecanismo de acção deste composto. Assim, o presente estudo procurou investigar o efeito da estrona em aorta de ratos, verificando seu efeito em induzir o relaxamento vascular e modular a via de sinalização dependente do óxido nítrico (NO), e ainda o papel dos receptores de estrogênios, comparando com os efeitos promovidos pelo 17β- estradiol. Os animais utilizados neste estudo foram ratos Wistar com 12 semanas de idade, os quais foram utilizados para realização da reatividade vascular em banho de órgãos isolados. Para os protocolos experimentais, curvas de concentraçãoresposta (0,1-100μM) foram feitas para a estrona ou para o 17β-estradiol e as tensões isométricas gravadas. Os mecanismos envolvidos no efeito induzido pela estrona foram determinados através da incubação de inibidores farmacológicos e comparado ao efeito do 17β-estradiol, que tem seu efeito vascular bem caracterizado. Observou-se que a estrona promove efeito vasorelaxante em aorta torácica de ratos, e que o relaxamento vascular promovido por ela é dependente do endotélio e do receptor de estrogênios. Após ativação do receptor de estrogênios, este ativa as vias de sinalização PI3K e Ca2+-CaM que posteriormente ativam a via NO/GMPc. Estes resultados contribuem para o melhor entendimento do papel da estrona em preparações de estrogênios conjugados equinos (CEE), que pode estar associado aos efeitos de benefícios dos estrogênios na terapia CEE.
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Tasci, Arzu Gul. "Biomechanical Evaluation Of Effects Of Estrogen, Selective Estrogen Receptor Modulator Drugs And Vitamin K2 On Osteoporotic Bone." Master's thesis, METU, 2004. http://etd.lib.metu.edu.tr/upload/12605451/index.pdf.
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In this study different bioactive agents were used to investigate their single and combined effects on biomechanical properties of osteoporotic bone.
Estrogen, the most common hormon replacement therapy (HRT) agent, was used in single and combined with raloxifen, a well known osteoporosis drug. Despite their high clinical uses, they have not been tried before, in combination. They act as agonist of each other in bone and antagonist of each other in uterus and mammary glands. Hence it was expected to prevent HRT side effects by using combinations while enhancing the healing on osteoporotic bone. So, the study was designed to see the interaction effects of these two agents on bone and uterus, to observe the mechanical behaviour upto fracture, and to investigate the bone mechanical properties by strain gauges and bending theory with ovariectomized rat model.
Second approach to osteoporosis treatment, VitK2 was chosen to be used alone or in combination with raloxifen in same model. Although recent studies mentioned
the effects of VitK2 on bone, its rebuilding or repair effect was not completely established. So, VitK2-bone relation was aimed to be clarified with the project.VitK2 raloxifen combination was also a new study, that has not been carried out so far.
As a result of mechanical tests, it was found that E+R combination is the most effective treatment. All treatment’
s were resulted in numerically (though not statistically significant) higher values on femur mechanical properties, and significantly better on tibia compared to the untreated controls. VitK2 performs well in energy absorption upto fracture, but worse in others (PL, YL etc.) compared to other treatments indicating that it plays a specific role in modifying bone structure thus, rendering bone stronger under high stress. However, similar to estrogen case, its combination with raloxifen performs better than its individual administration. With combinations it was aimed to reduce the adverse effects of estrogen on uterus and mammary glands by using raloxifen. This idea appears to be achieved with better histological results of uterus in combinations than estrogen groups. Additionally it was observed that direct strain data obtained by strain gauge experiments can be more informative than theoretical model in calculating modulus of elasticity, and shown that shear contribution can be neglected if depth/span ratio and set up dimensions properly chosen. Biochemical analysis of the blood showed an increment in bone formation (ALP activity) compared to both controls. ALP activity was the highest in R group, which was lower in combinations. Thus existence of a different mechanism in osteoporotic bone repair in combinations was suggested.