The C57 BL/KsJ db/db mouse is obese, hyperglycemic, hyperinsulinemic and serves as a model for noninsulin dependent diabetes mellitus (NIDDM). This study reports a dysfunction in the pituitary-thyroid axis and apparent peripheral resistence to thyroid hormones due to a reduction in T3 receptor binding. Diabetic mice have subnormal serum T4 concentrations and supranormal T3 concentrations which are most pronounced between 8 and 10 weeks of age. Thyroid glands of diabetic animals appear hypoactive histologically. Serum TSH concentrations approximate those found in normal mice. In vitro studies show that thryroid glands from diabetic animals are responsive to TSH. Pituitary glands from the same animals hypersecrete TSH and are responsive to TRH. Ultrastructural analysis of pituitary thyrotropes from diabetic mice indicate that these cells are hypersecretory and may be under chronic stimulation by TRH. Diet restriction maintains diabetic mice at a normal total body weight but these animals still possess abnormally large fat deposits. The thyroid hormone profile of these mice appears normal as does the histological appearance of the thyroid gland. Similarly, the blockade of peripheral deiodination by daily injection of iopanoic acid returns the thyroid hormone profile to normal.

Orientador: Célia Regina Nogueira / Resumo: Os hormônios tireoidianos (HTs) são fundamentais para o crescimento e desenvolvimento de vários órgãos e tecido. A fonte de HTs é a glândula tireoide, que faz parte do eixo hipotálamo-hipófise-tireoide e produz, principalmente, triiodotironina (T3) e tiroxina (T4). A disfunção tireoidiana é frequentemente associada com mudanças no apetite e peso corporal, que levam a alterações em parâmetros metabólicos, desempenhando papel importante na regulação do metabolismo e do tecido adiposo. A relação entre obesidade e distúrbios na tireoide vem sendo muito estudada, porem ainda não é bem estabelecida. A Organização Mundial de Saúde (OMS) reconhece a obesidade como um importante problema de saúde pública, que afeta crianças, adolescentes e adultos. Com embasamento na literatura, a partir dos modelos estudados pelo nosso grupo e a fim de ampliar as pesquisas nesta área, o objetivo do nosso estudo foi avaliar a influência do hormônio tireoidiano sobre o perfil nutricional, metabólico e hormonal de ratos obesos. Foram utilizados Ratos Wistar machos, com 60 dias, foram distribuídos em dois grupos: controle (C; n=24) e obeso (OB; n=24). Os ratos C receberam ração padrão e os OB ração ocidental. Posteriormente, na 43º semana após o início das dietas os animais de ambos os grupos foram realocados em 2 novos grupos para início do tratamento hormonal, formando neste momento 4 grupos experimentais (C; n=12, CT; n=12, OB; n=12, OBT; n=12). A gordura corporal total foi realizada pela somatória do... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Thyroid hormones (HTs) are key to the growth and development of various organs and tissue. The source of HTs is the thyroid gland, which is part of the hypothalamicpituitary-thyroid axis and produces, mainly, triiodothyronine (T3) and thyroxine (T4). Thyroid dysfunction is often associated with changes in appetite and body weight, leading to changes in metabolic parameters, playing an important role in the regulation of metabolism and adipose tissue. The relationship between obesity and thyroid disorders has been much studied but is still not well established. The World Health Organization (WHO) recognizes obesity as an important public health problem that affects children, adolescents, and adults. The objective of our study was to evaluate the influence of thyroid hormone on the nutritional, metabolic and hormonal profile of obese rats, based on the models studied by our group and in order to broaden the research in this area. Male Wistar rats, 60 days old, were used in two groups: control (C; n = 24) and obese (OB; n = 24). C rats received standard ration and Western rations. Later, at the 43rd week after the beginning of the diets, the animals of both groups were relocated into 2 new groups to start the hormonal treatment, forming at this moment 4 experimental groups (C; n = 12, CT; n = 12, OB; n = 12, OBT; n = 12). The total body fat was performed by the sum of the epididymal, retroperitoneal, visceral deposits and the obesity defined by the adiposity index. The nutrition... (Complete abstract click electronic access below) / Mestre

Thyroid hormones (TH) exert their multitude of effects on body development, growth and metabolism largely via transcriptional regulatory pathways. TH-induced transcription is controlled by receptors present in the cell nucleus, therefore extracellular TH must first cross the plasma membrane to gain entry into the cell. The exact mechanisms of TH transport across the plasma membrane are only beginning to be clarified, but it is likely that transport may be an important control step for the effects of TH on transcription. Members of the recently cloned organic anion transporting polypeptide (OATP) family have been shown to transport TH. Inhibitor studies indicate that both the aromatic amino acid System T-type transporter, and the broad scope neutral amino acid transporter System L are mediators of TH uptake into various cell types. However cloned amino acid transporters have not been studied to demonstrate directly whether they can accept TH as substrates.

Cave (Petrochelidon fulva) and cliff swallows (Petrochelidon pyrrhonota) were collected along the Rio Grande and evaluated as potential indicators of environmental contamination. The Rio Grande receives toxic substances from agricultural, industrial, municipal, and non-point sources; consequently, high levels of contaminants have been detected in birds, mammals, fishes and sediments. Swallows were obtained from 8 sites between Brownsville and El Paso, as well as from a reference site in Burleson County, 320 miles north of the nearest site of the Rio Grande. Blood samples were analyzed by flow cytometry, a technique that allows the detection of DNA damage in blood and other tissues. Plasma samples were analyzed for thyroid hormones using a radioimmunoassay technique. Organochlorines and trace metal analysis was limited to a few samples. DDE and PCB levels were below levels known to cause reduced hatching, embryo mortality, and deformities, Hg, Pb, and As were below detection, and Se, Ni and Cr concentrations were lower than levels known to cause harm in birds. Neither species showed sex-related differences in chromosome damage. Cave swallows from the Del Rio area had the highest levels of DNA variation, which may be indicative of DNA damage, possibly from PAHs exposure. Previous studies indicate that sediment samples from tributaries near Del Rio have high levels of chromium compared to other sites along the Rio Grande. A significant increase in DNA variation between sampling years was detected in cave swallows from Llano Grande Lake. Wildlife samples collected from Llano Grande Lake have recorded high levels of DDE and PCBs; in addition, this urban/agricultural contaminant sink appears to be affected by PAH exposure. T3 levels were below the detection limit of the radioimmunoassay. There were no gender related differences in T4 levels in cave swallows. Cave swallows sampled from Laredo had significantly higher T4 levels than those from birds at other sites during 1999. It was not possible to determine thyroid hormone disruption in plasma samples. Thyroid hormone and flow cytometry data were useful in establishing baseline data. Areas of concern based on genotoxic data include Llano Grande Lake, Del Rio, and El Paso.

This study investigated the effect of chronic alcohol exposure on the responses of the maternal hypothalamus-pituitary adrenal axis (HPA-axis) and thyroid hormones throughout gestation using an ovine model. Maternal plasma concentrations of ACTH, cortisol and the thyroid hormones T3, free T4 and total T4 were determined in response to infusion of 0.75, 1.25 and 1.75 g/kg alcohol. Maternal endocrine responses to alcohol administration have been investigated before in rodent models. However, this is the first study using a large animal model (sheep), in which all three human trimester equivalents occur in utero. Different concentrations of alcohol were administered intermittently from gestational day 4 to 132 in a pattern that modeled human binge drinking during pregnancy. Maternal blood samples were collected on specific days (GD 6, 40, 90, 132) and at multiple time-points (0, 0.5, 1, 1.5, 2, 6, 24 hours) and were analyzed to determine blood alcohol concentrations (BACs) and ACTH, cortisol, free T4, total T4 and T3 plasma concentrations. Alcohol readily permeates the placenta and can directly affect fetal cells and tissues. Alcohol also causes endocrine imbalances in the mother and interferes with maternal-fetal hormonal interactions and the mother’s ability to maintain a healthy pregnancy, thus also indirectly affecting fetal development. Sheep receiving either 0.75, 1.25 or 1.75 g/kg alcohol achieved peak BAC values of 93 + 5, 126 + 5 and 183 + 5 respectively. Alcohol exposure resulted in increased plasma ACTH and cortisol concentrations peaking at 2 hours after beginning of the infusion and returning to baseline values at 6 hours after beginning of the infusion. There was no effect of alcohol on any of the plasma thyroid hormone concentrations. Thyroid hormone concentrations changed as a result of progressing pregnancy. Plasma concentrations of total T4 and free T4 were higher on gestational days 6 and 40 compared to GDs 90 and 132, and plasma T3 concentrations were highest on GD 6. The results of this study show that alcohol stimulates the HPA-axis in a dose dependent fashion in pregnant sheep. The response of the HPA-axis to repeated alcohol exposure throughout gestation remained unchanged. Alcohol exposure did not affect the release of thyroid hormones. Thyroid hormone concentrations changed during pregnancy in sheep in a manner similar to changes observed in pregnant women.

Cave (Petrochelidon fulva) and cliff swallows (Petrochelidon pyrrhonota) were collected along the Rio Grande and evaluated as potential indicators of environmental contamination. The Rio Grande receives toxic substances from agricultural, industrial, municipal, and non-point sources; consequently, high levels of contaminants have been detected in birds, mammals, fishes and sediments. Swallows were obtained from 8 sites between Brownsville and El Paso, as well as from a reference site in Burleson County, 320 miles north of the nearest site of the Rio Grande. Blood samples were analyzed by flow cytometry, a technique that allows the detection of DNA damage in blood and other tissues. Plasma samples were analyzed for thyroid hormones using a radioimmunoassay technique. Organochlorines and trace metal analysis was limited to a few samples. DDE and PCB levels were below levels known to cause reduced hatching, embryo mortality, and deformities, Hg, Pb, and As were below detection, and Se, Ni and Cr concentrations were lower than levels known to cause harm in birds. Neither species showed sex-related differences in chromosome damage. Cave swallows from the Del Rio area had the highest levels of DNA variation, which may be indicative of DNA damage, possibly from PAHs exposure. Previous studies indicate that sediment samples from tributaries near Del Rio have high levels of chromium compared to other sites along the Rio Grande. A significant increase in DNA variation between sampling years was detected in cave swallows from Llano Grande Lake. Wildlife samples collected from Llano Grande Lake have recorded high levels of DDE and PCBs; in addition, this urban/agricultural contaminant sink appears to be affected by PAH exposure. T3 levels were below the detection limit of the radioimmunoassay. There were no gender related differences in T4 levels in cave swallows. Cave swallows sampled from Laredo had significantly higher T4 levels than those from birds at other sites during 1999. It was not possible to determine thyroid hormone disruption in plasma samples. Thyroid hormone and flow cytometry data were useful in establishing baseline data. Areas of concern based on genotoxic data include Llano Grande Lake, Del Rio, and El Paso.

Thesis--University of Göteborg. / Includes bibliographical references (p. 26-29).

Thesis (M.Sc.)--York University, 2006. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR29625

Thesis (Ph. D.)--University of Florida, 2004. / Title from PDF title page (viewed on July 3, 2005). Includes vita. Includes bibliographical references (p. 161-178).

Thesis--University of Göteborg. / Includes bibliographical references (p. 26-29).