Neste projeto investigou-se o uso de três técnicas: (i) eletrólise, (ii) fotoeletrocatálise e (iii) fotólise, na degradação do hormônio estradiol, comumente encontrado nos esgotos domésticos, e que geram sérias preocupações com a ação nefasta que podem provocar na vida selvagem e humana. Os ensaios eletroquímicos foram realizados sobre eletrodos de platina e carbono vítreo. A técnica de fotoeletrocatálise foi aplicada empregando-se placas de titânio recobertas com nanocamadas de TiO2. Como fonte de radiação ultravioleta utilizou-se uma lâmpada de vapor de mercúrio de 125 W tanto na fotoeletrocatálise como na fotólise. Através dos estudos da oxidação do estradiol por voltametria cíclica, sobre os eletrodos acima mencionados, foi possível definir o seu potencial de oxidação em soluções de KCl e tampão fosfato (pH 7), sobre platina e carbono vítreo. Estes parâmetros serviram de base para a realização das eletrólises sob condições controladas. A fotoeletrocatálise do estradiol foi realizada sobre Ti/TiO2 preparado por técnica sol-gel e se mostrou muito mais efetiva que a eletrólise eletrolítica. Finalmente, a fotólise também foi testada empregando-se apenas a lâmpada de vapor de mercúrio. Neste último caso a degradação do estradiol foi ligeiramente inferior que aquela observada por fotoeletrocatálise. Identificou-se que em soluções de KCl há a formação de hipoclorito, o que auxilia o processo oxidativo do estradiol. Espectroscopia de UV-vís e cromatografia líquida (HPLC) foram empregadas para acompanhar os processos de degradação. Apesar de ter sido observado o surgimento de bandas e picos cromatográficos devidos aos produtos formados, não foi possível identifica-los. / In this project the use of three techniques was investigated: (i) electrolysis, (ii) photoelectrocatalysis and (iii) photolysis, in the degradation of the hormone estradiol, commonly found in the domestic sewers. This hormone can generate serious concerns with a disastrous action that can provoke in the wild and human life. The electrochemistry studies were accomplished on platinum and glassy carbon electrodes. The photoelectrocatalysis technique was applied using titanium plate covered with nanolayers of TiO2. As a source of ultra-violet radiation was used a lamp bulb of mercury vapor of 125 W for the photoelectrocatalysis as also in the photolysis. Through the studies of the oxidation of the estradiol by cyclic voltammetry, on the electrodes above mentioned, it was possible to define the oxidation potential of the organic specie in both solutions, KCl and phosphate buffers (pH 7), for platinum and glassy carbon. These parameters served as base for the realization of the electrolysis under controlled conditions. The photoelectrocatalysis of the estradiol was accomplished on Ti/TiO2 prepared by sol-gel technique and it was shown much more effective than the electrolyitc electrolysis. Finally, the photolysis was also tested being just used the mercury vapor lamp. In this last case the degradation of the estradiol was lightly inferior to that observed by photoelectrocatalysis It was identified that in solutions of KCl there is the hypochlorite formation, what aids the oxidation of the estradiol. Spectroscopy of UV-vis and high performance liquid chromatography (HPLC) were used to accompany the degradation processes. In spite of the appearance of bands and chromatographyc peaks owed to the formed products having been observed, however, it were not possible identify them.

O GLUT4 (gene Slc2<font face=\"symbol\">a4) é responsável pela captação de glicose sob estímulo insulínico, e alterações na sua expressão se relacionam à resistência à insulina (RI). Variações na concentração de estradiol (E2) estão relacionadas a RI e menor expressão deste transportador, mecanismo que pode ser mediado pelo fator transcricional NF<font face=\"symbol\">k-B, um repressor de Slc2<font face=\"symbol\">a4. Avaliou-se em células 3T3-L1 a regulação da expressão de Slc2<font face=\"symbol\">a4/GLUT4, a atividade de ligação de NF<font face=\"symbol\">k-B e a captação de glicose pelo E2 e o papel de ESR1 (isoforma 1 do receptor de E2) nesta regulação. Tratou-se as células por 1 dia com E2 e PPT (agonista de ESR1). O PPT aumentou a expressão de Slc2<font face=\"symbol\">a4/GLUT4 na ausência ou presença de E2 bem como a captação de glicose e diminuiu a atividade de ligação de NF<font face=\"symbol\">k-B. Os resultados apresentados demonstram que o E2, atuando via ESR1 aumenta a expressão de Slc2<font face=\"symbol\">a4/GLUT4, efeitos estes parcialmente mediados por NF<font face=\"symbol\">k-B, resultando em alteração na captação de glicose. / GLUT4 (gene Slc2<font face=\"symbol\">a4) is responsible by insulin-induced glucose uptake and alterations in its expression are related to insulin resistance (IR). Variability in estradiol levels (E2) is related with IR and lower glucose transporter expression and this mechanism can be mediated by transcriptional factor NF<font face=\"symbol\">k-B, which is an Slc2<font face=\"symbol\">a4 repressor. Our aim was to evaluate in 3T3-L1 adipocytes the role of E2 in Slc2<font face=\"symbol\">a4/GLUT4 expression, NF<font face=\"symbol\">k-B binding activity and glucose uptake as well as the ESR1 (estrogen receptor 1) role in this regulation. For this, 3T3-L1 cells were treated for 1 day with E2 and PPT (ESR1-agonist). PPT enhanced Slc2<font face=\"symbol\">a4/GLUT4 expression in the absence or presence of E2 as well as the glucose uptake and decreased NF<font face=\"symbol\">k-B binding activity. Our results show that E2 increases Slc2<font face=\"symbol\">a4/GLUT4 expression via ESR1 and this effect is partially mediated by NF<font face=\"symbol\">k-B, and allow parallel changes in glucose uptake.

Orientador: Laura Sterian Ward / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T14:43:40Z (GMT). No. of bitstreams: 1 Bufalo_NatassiaElena_D.pdf: 3667340 bytes, checksum: 4934d4d9652dfe1e6d10650634ac9866 (MD5) Previous issue date: 2012 / Resumo: Tanto a Doença de Graves (DG) como o Carcinoma Diferenciado da Tiroide (CDT) são patologias de etiologia multifatorial e envolvem uma interação entre meio ambiente e fatores genéticos de predisposição. Ambas apresentam nítida preferência pelo sexo feminino. Por isso, variações no metabolismo do estrógeno poderiam estar associadas a esta preferência, pois, seus metabólitos podem causar dano ao material genético. Os objetivos foram determinar a influência dos polimorfismos dos genes CYP17A1, HSD-17?1, CYP1A1, CYP1A2, CYP1B1, COMT e SULT1E1 no risco para a DG e para o CDT. Para tanto, foi estudado 282 pacientes com DG (234 mulheres e 48 homens; 39,80±11,69 anos), 292 pacientes com CDT (248 mulheres e 44 homens; 42,23±14,81 anos), comparados com 308 controles (246 mulheres e 62 homens; 36,86±12,95 anos). Para o estudo dos polimorfismos, utilizou-se a técnica TaqMan SNP Genotyping. Alterações polimórficas nos genes CYP17A1 (p=0,0421), CYP1A1 m1 (p=0,0328), CYP1A2*1F (p=0,0085), CYP1B1 códon 119 (p<0,0001) e CYP1B1 códon 432 (p=0,0059) aumentam a suscetibilidade ao CDT. Já as alterações polimórficas nos genes CYP1A1 m1 (p<0,0001), CYP1B1 códon 119 (p<0,0001) e CYP1B1 códon 432 (p=0,0208) aumentam a suscetibilidade à DG. Entre os pacientes com DG, mulheres heterozigotas para CYP1A1 m1 apresentam maior número de gestações (p=0,0071), paridade (p=0,0204) e abortos (p=0,0012), além de bócio mais pesado (gramas) (p=0,0082). Já entre os pacientes com CDT, mulheres heterozigotas para CYP17A1 apresentam maior número de abortos (p=0,0150). A herança heterozigota para o gene CYP1A2*F está relacionada com idade mais precoce (p=0,0073) para o surgimento do CDT. A herança do polimorfismo do gene CYP1B1 códon 119 está associada ao hábito tabagista (p=0,0269), uso de reposição hormonal (p=0,0197) e presença de menopausa (p=0,0317) para pacientes com CDT. Já para pacientes com DG, este polimorfismo se correlaciona com concentrações mais elevadas de T4livre (p=0,0409) e TRAb (p=0,0465). A herança em heterozigose do gene CYP1B1 códon 432 foi mais frequente em pacientes com carcinoma papilífero do que nos pacientes com carcinoma folicular (p=0,0243), além da herança em homozigose se correlacionar com maior idade (p=0,0204) e com sobrepeso (p=0,0392) em pacientes com DG. Mulheres com o genótipo homozigoto polimórfico para CYP1B1 códon 453 se correlacionam com uso de anticoncepcional (p=0,0332) no CDT. Maior número de gestações (p=0,0256) e de paridade (p=0,0141) se correlacionam com mulheres homozigotas para o gene HSD-17?1 na DG. Concluímos que os fatores exógenos e endógenos ligados aos hormônios sexuais possuem considerável variabilidade individual, devido aos polimorfismos da via de metabolização do estrógeno. As diferentes heranças polimórficas individuais, que são atribuídas aos polimorfismos dos genes codificadores de enzimas envolvidas na produção, metabolização e eliminação do estrógeno devem definir subpopulações de mulheres que são afetadas pela maior exposição aos estrógenos e aos seus metabólitos, os quais afetam o crescimento celular e podem induzir danos celulares carcinogênicos a ativar a resposta imune / Abstract: Graves' disease (GD) and Differentiated Thyroid Carcinoma (DTC) are multifactorial diseases and involved an interaction between environmental factors and genetic predisposition. Both diseases have preference for female. Therefore, variations in estrogen metabolism could be associated with that preference, because its metabolites can cause damage to genetic material. The objectives were to determine the influence of polymorphisms of genes CYP17A1, HSD-17?1, CYP1A1, CYP1A2, CYP1B1, COMT and SULT1E1 at the susceptibility for GD and DTC. We studied 282 patients with GD (234 females and 48 males, 39.80±11.69 years old), 292 patients with DTC (248 women and 44 men, 42.23±14.81 years old), compared with 308 controls (246 women and 62 men, 36.86±12.95 years old). TaqMan SNP genotyping technique was used to study the polymorphisms. Polymorphisms in CYP17A1 (p=0.0421), CYP1A1 m1 (p=0.0328), CYP1A2*1F (p=0.0085), CYP1B1 codon 119 (p<0.0001) and CYP1B1 codon 432 (p=0.0059) increases the susceptibility to DTC. The polymorphisms of CYP1A1 m1 (p<0.0001), CYP1B1 codon 119 (p<0.0001) and CYP1B1 codon 432 (p=0.0208) increases the susceptibility for GD. Women with GD have a higher number of pregnancies (p=0.0071), parity (p=0.0204), abortions (p=0.0012) and goiter heavier (grams) (p=0.0082) when heterozygous for CYP1A1 m1. Among patients with DTC, women heterozygous for CYP17A1 highest number of abortions (p=0.0150). The inheritance in heterozygous for the CYP1A2*F are correlated to younger age (p=0.0073) for the susceptibility to DTC. The inheritance of polymorphism of the CYP1B1 codon 119 gene is associated with smoking (p=0.0269), use of hormone replacement therapy (p = 0.0197) and menopausal status (p=0.0317) for patients with DTC. However, for patients with GD, this polymorphism correlated with higher concentrations of FT4 (p=0.0409) and TRAb (p=0.0465). The inheritance in heterozygous for CYP1B1 codon 432 gene was more frequent in patients with papillary carcinoma than in patients with follicular carcinoma (p=0.0243) and the homozygous inheritance correlate with older (p=0.0204) and overweight (p=0.0392) in patients with GD. Women with the inheritance for polymorphic homozygous for CYP1B1 codon 453 correlated with contraceptive use (p=0.0332) in the DTC. Increased number of pregnancies (p=0.0256) and parity (p=0.0141) correlated with women homozygous for the HSD -17?1 gene in GD. We conclude that exogenous and endogenous factors related to sex hormones have considerable individual variability due to polymorphisms of the estrogen metabolic pathway. The different polymorphic individual heritages, which are attributed to the polymorphisms of genes encoding enzymes involved in the production, metabolism and excretion of estrogen should define subpopulations of women who are affected by increased exposure to estrogens and their metabolites, which affect cell growth and can induce cellular damage carcinogens activate the immune response / Doutorado / Ciencias Basicas / Doutor em Clínica Médica

Orientadores: Sebastião Roberto Taboga, Fernanda Cristina Alcântara dos Santos / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-20T16:21:42Z (GMT). No. of bitstreams: 1 Zanatelli_Marianna_M.pdf: 26022421 bytes, checksum: 23b2b9c60198cc10c0b2a25abeb3f837 (MD5) Previous issue date: 2012 / Resumo: A próstata feminina é uma glândula funcionalmente ativa encontrada em diversas espécies de mamíferos, incluindo humanos e roedores. Em fêmeas adultas de gerbilos, a próstata apresenta localização parauretral, exibindo íntimo contato com a parede da uretra média. Esta glândula é homóloga à próstata ventral de roedores machos, sendo formada por um conjunto de ácinos e ductos inseridos em um estroma fibromuscular. O estudo da morfofisiologia prostática nas fases do ciclo estral tem demonstrado que a próstata feminina é influenciada pelas oscilações nos níveis séricos de estradiol e progesterona, com picos nas fases de estro e diestro II, respectivamente. Sendo assim, este trabalho teve como objetivo avaliar o efeito da administração combinada e prolongada de estradiol e progesterona sobre a próstata de fêmeas de gerbilo ovariectomizadas. A ovariectomia causou regressão glandular e diminuição da atividade secretora, aspectos sugeridos, entre outros, pela diminuição da massa prostática e a quase ausência de secreção glicoprotéica. Essas mudanças estão ligadas à supressão hormonal causada pela retirada dos ovários. A posterior reposição pelo estradiol e pela progesterona em associação mostrou uma grande recuperação da estrutura e fisiologia geral da próstata, evidenciada pelo aumento da altura do epitélio, da massa prostática e da atividade secretora. Os níveis hormonais aumentaram, justificando a recuperação da glândula, porém não atingiram o mesmo perfil observado no grupo controle. Também foram avaliadas as alterações na expressão de AR, ER?, ER? e no indicador de proliferação celular, PCNA, que mostraram maior imunorreatividade e maior número de células proliferativas no grupo tratado. A integridade da próstata não se relaciona apenas com os níveis de estrógeno e progesterona, mas também com o balanço cíclico entre esses hormônios no organismo feminino. Por fim, estudos sobre as ações do estrógeno e da progesterona na próstata podem abrir caminho para o desenvolvimento de tratamentos de importantes doenças prostáticas, as quais acometem tanto indivíduos do sexo masculino quanto do sexo feminino / Abstract: The female prostate is a gland functionally active found in several species of mammals, including humans and rodents. In adult female gerbils, the prostate presents paraurethral location, showing close contact with the wall of the median urethra. This gland is homologous to the ventral prostate of male rodents and it is formed by a set of acini and ducts embedded in a fibromuscular stroma. The study of prostatic morphophysiology in the estrous cycle phases has shown that the female prostate is influenced by fluctuations in serum of estradiol and progesterone, with peaks in estrous and diestrus II phases, respectively. Therefore, this study aimed to evaluate the effect of combined and prolonged administration of estradiol and progesterone on the prostate of ovariectomized female gerbil. Ovariectomy caused regression and decreased glandular secretory activity, aspects suggested by the shrinkage of the prostate and the almost absence of glycoprotein secretion. These changes are linked to hormonal supply caused by the ovaries removal. The subsequent replacement by estradiol and progesterone in combination showed a greater recovery of the structure and general physiology of the prostate, as evidenced by increased epithelial height, prostatic mass and secretory activity. The hormone levels increased, justifying the recovery of the gland, but did not achieve the same profile observed in the control group. We also evaluated the changes in the expression of AR, ER?, ER? and the cell proliferation marker, PCNA, which showed increased immunoreactivity and increased number of proliferating cells in the treated group. The integrity of the prostate is not only related to the levels of estrogen and progesterone, but also with the cyclical balance between these hormones in the female body. Finally, studies about the actions of estrogen and progesterone in prostate may be the starter for the development of treatments for important prostate diseases, which affect both males and females / Mestrado / Biologia Celular / Mestre em Biologia Celular e Estrutural

Pituitary hormones are known to alter sex steroid receptor levels in the liver, and possibly the actions of the steroids as well. Recently, two classes of estrogen binding proteins have been characterized in male rat hepatic cytosol: a high affinity, low capacity estrogen receptor, and a lower affinity, higher capacity sex steroid binding component (moderate affinity component). It is of interest that the moderate affinity component binds both androgens and estrogens. A high affinity, low capacity androgen receptor has not been convincingly demonstrated in rat hepatic cytosol. Therefore, we have investigated the relationship of the moderate affinity component to sex steroid modulation of hepatic aryl hydrocarbon hydroxylase (AHH) activity as a possible control mechanism. Because of the sexual dimorphism for hepatic drug and steroid metabolism known to occur in rat liver, we chose this model to study. We have shown that no sex difference exists for the binding of pH]-estradiol to the estrogen receptor from either immature or adult rats. However, the moderate affinity component does exhibit a sex difference. We did not detect binding to the moderate affinity component in adult female or immature rats of either sex. This site could normally only be measured in the adult male. These findings were consistent with the age and sex dependent elevation of male AHH activity. We have also observed that gonadectomy of the male reduced the levels of AHH activity and the capacity of the moderate affinity component in a testosterone reversible fashion. These results were obtained using either unlabeled estradiol or dihydrotestosterone (DHT) as competitors for [³H]-estradiol binding. Administration of mestranol reduced AHH activity and the capacity of the moderate affinity component in the male. The moderate affinity component was not detected in the pseudoherma-phroditic rat which resembled the female, rather than the male, with respect to control and induced AHH activity. Hypophysectomy of the female resulted in an increase in AHH activity and detection of the moderate affinity component. Hypophysectomy of the male reduced both the capacity of the moderate affinity component and AHH activity. Unlike the gonadectomized male, testosterone had no restorative effect on the levels of AHH activity or the capacity of the moderate affinity component in the hypophy-sectomized rat. Continuous infusion of rat growth hormone (rGH) reversed the effect of hypophysectomy on the increased AHH activity and capacity of the moderate affinity component in the female. Administration of rGH to the hypophysectomized male abolished the detection of the moderate affinity component and reduced AHH activity to control female levels. This suggested rGH may be the pituitary hormone involved in production of the female level of metabolism. The effects of prolactin were not as clear. Therefore, we have demonstrated the modulation of AHH activity by peripheral sex steroids, and the regulation of these parameters by rGH. We have shown, the capacity of the moderate affinity component to vary in a manner that paralleled changes in hepatic AHH activity in different physiological models. Changes in the estrogen receptor were not found to be consistent with changes in AHH activity in these models. We conclude that the moderate affinity component is comparable to the male hepatic cytosolic DHT-binding protein. Furthermore, this component is associated with sex steroid action on hepatic AHH activity in the male rat. Interestingly, we have also shown this component as well as the estrogen receptor, to bind polycyclic aromatic hydrocarbons. Both 3-methylcholanthrene and benzo[a]pyrene competed for [³H]-estradiol binding to the estrogen receptor and moderate affinity component. In addition, dioxin congeners demonstrated specificity for the estrogen receptor in the female. However, this was not observed for the estrogen receptor or moderate affinity component in the male. The significance of this is presently unclear. / Pharmaceutical Sciences, Faculty of / Graduate

Submitted by Reginaldo Soares de Freitas (reginaldo.freitas@ufv.br) on 2018-04-25T12:38:47Z No. of bitstreams: 1 texto completo.pdf: 4136291 bytes, checksum: f66711234c1f446cfe714838bcc10b9f (MD5) / Made available in DSpace on 2018-04-25T12:38:47Z (GMT). No. of bitstreams: 1 texto completo.pdf: 4136291 bytes, checksum: f66711234c1f446cfe714838bcc10b9f (MD5) Previous issue date: 2018-02-23 / Fundação de Amparo à Pesquisa do Estado de Minas Gerais / As folhas e raízes de Pfaffia glomerata são usadas como afrodisíacos, tranquilizantes e antirreumáticos. Devido à ausência de dados científicos experimentais faz-se necessário estudos que identifiquem suas propriedades medicinais. Baseado nisso objetivou-se avaliar o efeito de extrato hidroalcoólico da raiz de P. glomerata (BGE) sobre o parênquima testicular, espermáticos e fertilidade. Camundongos adultos (n=60) foram divididos em controle (água), Citrato de sildenafila (7mg/kg) e 3 grupos recebendo doses diárias (100, 200 e 400 BGE mg/Kg) e uma dose intermitente (200 BGE mg/Kg a cada três dias) por 42 dias. Após a ingestão do extrato, houve redução na proporção de túbulo e epitélio seminíferos, aumento do volume de túnica própria e redução do número de células de Sertoli, sem prejuízo a produção espermática. Entretanto, o BGE promoveu morte celular e alteração na frequência de estádio dos túbulos, além do aumento de óxido nítrico. Verificou-se também aumento do percentual e volume de vasos sanguíneos e espaço linfático, redução da testosterona, aumento do estradiol e morte de células de Leydig. Observou-se aumento de corpos cavernosos, aumento de colágeno, redução do músculo liso e aumento do óxido nítrico peniano. O tratamento causou ainda redução no número e viabilidade de espermatozoides, estes apresentavam altos índices de patologias, como espaços vacuolares, degeneração e descamação. Baixo percentual de espermatozoides com membrana íntegra e alterações na motilidade, leva ainda a perdas embrionárias. O princípio de ação do extrato baseia-se na produção de NO, atuando sobre os vasos sanguíneos aumentando os corpos cavernosos. O tratamento leva ainda redução do músculo liso peniano, danos nas células de Leydig, acumulo de gotículas de lipídios no seu citoplasma levando, inclusive, à morte da célula de Leydig e o aumento do NO. O extrato atua também aumentando ROS, culminando com danos de DNA, que leva a perdas embrionárias. Porém embora o quadro leve a aparente redução da atividade sexual, o aumento de estradiol e colágeno é uma forma de compensação e assim da manutenção da atividade sexual. Assim, o ginseng brasileiro tem ação afrodisíaca, porém com efeitos colaterais na produção de testosterona e na viabilidade das células germinativas. / The leaves and roots of Pfaffia glomerata are used as aphrodisiacs, tranquillizers and antirheumatics. Due to the lack of experimental scientific data, studies are necessary to identify its medicinal properties. Based on this the objective was to evaluate the effect of hydroalcoholic extract of the P. glomerata root (BGE) on the testicular parenchyma, spermatozoa and fertility. Adult mice (n = 60) were divided into control (water), sildenafil Citrate (7mg / kg) and 3 groups receiving daily doses (100, 200 and 400 BGE mg / kg) and an intermittent dose (200 BGE mg / kg every three days) for 42 days. After ingestion of the extract, there was a reduction in the proportion of seminiferous tubule and epithelium, increase of the own tunica volume and reduction of the number of Sertoli cells, without prejudice to sperm production. However, BGE promoted cell death and a change in tubule stage frequency, in addition to an increase in nitric oxide. There was also an increase in the percentage and volume of blood vessels and lymphatic space, reduction of testosterone, increase of estradiol and death of Leydig cells. There was an increase of cavernous bodies, increase of collagen, reduction of smooth muscle and increase of penile nitric oxide. The treatment also caused a reduction in the number and viability of spermatozoa, which presented high rates of pathologies, such as vacuolar spaces, degeneration and desquamation. Low percentage of spermatozoa with whole membrane and alterations in the motility, still leads to embryonic losses. The principle of action of the extract is based on the production of NO, acting on the blood vessels increasing the cavernous bodies. The treatment also leads to reduction of the penis smooth muscle, Leydig cell damage, accumulation of lipid droplets in its cytoplasm leading to Leydig cell death and increased NO. The extract also works by increasing ROS, culminating with DNA damage, leading to embryonic losses. However, although the picture leads to the apparent reduction of sexual activity, the increase of estradiol and collagen is a form of compensation and thus the maintenance of sexual activity. Thus, Brazilian ginseng has an aphrodisiac effect, but with side effects on testosterone production and germ cell viability.

The female sex hormone 17beta-estradiol, produced naturally in the body, seems to play an important role in the development of breast cancer, since (i) it can be activated to reactive metabolites, which are known to damage DNA and (ii) the stimulation of the estrogen receptor alpha by 17beta-estradiol enhances cell proliferation. Both processes together increase mutation frequency and subsequently lead to transformation of epithelial cells. Therefore, the aim of this work was to characterize the influence of polymorphisms and lifestyle factors on 17beta-estradiol metabolism in normal mammary gland tissue. [...] In sum, the tissue specific 17beta-estradiol metabolism was described in mammary gland tissue homogenate, whereas differences in proliferation of epithelial cells were only reflected in isolated epithelial cells. Factors associated with breast cancer risk (age, BMI and age-related changes in mammary gland morphology) were shown to affect 17beta-estradiol tissue levels. The 17beta-estradiol mediated genotoxicity was evaluated using bioinformatically calculated DNA adduct fluxes, which were predominately influenced by individual mRNA patterns rather than individual genotypes and (DNA adduct fluxes) were correlated with known breast cancer risk factors (age, parity, BMI and polymorphism of glutathione-S-transferase theta 1). / Das körpereigene, weibliche Geschlechtshormon, 17beta-Estradiol spielt eine wichtige Rolle bei der Brustkrebsentstehung, da (i) es zu reaktiven Metaboliten aktiviert werden kann, welche die DNA schädigen können und (ii) durch die Stimulation des Estrogenrezeptors alpha die Zellproliferation steigern kann. Beide Prozesse können dann zum Anstieg der Mutationsfrequenz und anschließender maligner Transformation von Epithelzellen führen. Deshalb war das Ziel dieser Arbeit, den Einfluss von Polymorphismen und der Lebensweise auf den gewebespezifischen 17beta-Estradiol-Metabolismus im normalen Brustdrüsengewebe zu untersuchen. [...] Zusammenfassend wurde der gewebespezifische 17beta-Estradiol-Metabolismus in der weiblichen Brustdrüse beschrieben. Unterschiede in der Proliferation von Epithelzellen wurden nur in mittels Laser-Mikrodissektion isolierten Epithelzellen widergespiegelt. Es wurde gezeigt, dass Faktoren, die mit einem verändertem Brustkrebsrisiko assoziiert sind (Alter, BMI und altersbedingte Veränderungen in der Brustdrüsenmorphologie), den 17beta-Estradiol-Gewebespiegel in der Brustdrüse beeinflussen. Die 17beta-Estradiol-vermittelte Genotoxizität wurde mittels bioinformatischer Berechnung der DNA-Adduktflüsse ausgewertet, welche vornehmlich von den individuellen mRNA-Mustern beeinflusst wurde statt von dem individuellen Genotyp. Die DNA-Adduktflüsse korrelierten mit bekannten Brustkrebsrisiko-Faktoren (Alter, Parität, BMI und Polymorphismus der Glutathion-S-Transferase theta 1).

Orientador: Renata Guimarães Moreira / Resumo: Este estudo investigou a influência da suplementação de vitamina A sobre a maturação ovariana de fêmeas do lambari-do-rabo-amarelo, Astyanax altiparanae. 580 fêmeas adultas foram distribuídas em 10 tanques de 750 litros, compondo 5 tratamentos (duplicata). Foi formulada uma ração com baixo nível de vitamina A, as rações foram suplementadas com 0; 1.800; 3.600; 7.200 e 14.400 UI/kg de ração. Após 8 dias de ajuste às condições experimentais com dietas comerciais, os peixes receberam uma dieta sem suplementação de vitamina A durante 16 dias, para a depleção dessas reservas e em seguida os animais foram alimentados por 60 dias com os diferentes tratamentos. Indicadores de maturação gonadal como concentração plasmática de 17β-Estradiol (E2), índice gonadossomático (IGS), fecundidade e histologia ovariana foram analisados aos 30 e 60 dias. Além destes, indicadores metabólicos, como o índice hepatossomático (IHS), viscerossomático (IVS) e concentração plasmática de lipídios totais, triglicérides, colesterol total e frações também foram analisados nestes momentos. Os diferentes níveis de vitamina A alterou o padrão de deposição ovariana desta vitamina. A manutenção nas condições experimentais promoveu a maturação ovariana, avaliada pela histologia do ovário e IGS. As variáveis fisiológicas mostraram que a manutenção das fêmeas com uma dieta composta integralmente por ingredientes vegetais, reduziu a concentração plasmática de lipídio e colesterol total e o nível mais elevado de suple... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study investigated the influence of vitamin A supplementation during the ovarian maturation of female lambari-do-rabo-amarelo, Astyanax altiparanae. 580 adult females were distributed in 10 tanks of 750 liters, composed by 5 treatments (duplicate). A basal diet with low level of vitamin A. The diet was supplemented with 0; 1.800; 3,600; 7,200 and 14,400 IU / kg of diet. After 8 days of adjustment to the experimental conditions with commercial diets, the fish received a diet without vitamin A supplementation for 16 days, for the depletion of these reserves and the animals were fed for 60 days with different treatments. Indicators of gonadal maturation, such as 17β-Estradiol (E2) plasma level, gonadosomatic index (GSI), fecundity and ovarian histology were analyzed at 30 and 60 days. Additionally, metabolic indicators such as hepatosomatic index (HSI), viscerosomal index (VSI) and plasma concentration of total lipids, triglycerides, total cholesterol and fractions were also analyzed at these periods. Vitamin A supplementation levels altered the deposition levels of this vitamin in the ovaries. The maintenance in the experimental conditions promoted ovarian maturation, evaluated by ovary histology and GSI. The physiological variables evidenced that the maintenance of these females in the experiment, with a diet composed entirely of vegetable ingredients, reduced the plasma levels of total lipids and cholesterol, and the higher level of supplementation (14,400 IU / kg) reduc... (Complete abstract click electronic access below) / Mestre

In cattle and sheep, a significant decrease in temperature has been noted prior to parturition. In the mare, similar temperature decreases have been documented, although results have been inconsistent when temperatures were taken rectally. One study reported a significant temperature decrease when using data from a radio transmitter inserted into the mare’s flank. The current study utilized nineteen Quarter Horse mares and one Thoroughbred mare, and was conducted from February to June 2006. Each mare had been previously implanted in the nuchal ligament with a microchip capable of reporting body temperatures. Blood collection and temperature recordings began 2 wk prior to each mare’s expected foaling date. Once the mare was estimated to be within 48 h of parturition, temperature was recorded every 3 h until parturition using both the microchip and rectal thermometer. Progesterone and estradiol 17-b were evaluated from daily blood samples from -10 to ± 5 d relative to foaling for determination of the relationship between these steroids and body temperature, time of foaling, birth weight and sex of foal. A significant decrease in rectal temperature (P < 0.05) was noted when the last temperature recorded was taken within 12h of parturition. Microchip data did not demonstrate any significant differences among readings before parturition. No significant difference was noted in the mean rectal temperature of all days relative to the sex of the neonate; however, microchip data showed mares carrying females to have a significantly (P < 0.05) higher mean rectal temperature of all days. Sex of the foal was not shown to be related to maternal concentrations of either progesterone or estradiol 17- b. A direct significant correlation between temperature and maternal plasma concentrations and progesterone and estradiol 17-b was found.

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xviii, 158 p. : ill. (some col.). Advisor: Young C. Lin, Veterinary Biosciences Graduate Program. Includes bibliographical references (p. 148-158).