O hormônio tireoideano (T3) é um potente regulador das funções cardíacas e musculares esqueléticas. Desse modo, o presente trabalho identificou o efeito de tal hormônio nas proteínas da banda M sarcomérica, as quais fazem parte das proteínas estruturais cardíacas e musculares esqueléticas. O T3 diminuiu a expressão da proteína M no coração, uma das proteínas da banda M, e agiu diretamente no gene dessa proteína M. No músculo esquelético, T3 aumentou a expressão de EH-miomesina no músculo sóleo e reduziu a expressão de proteína M no músculo extensor digital longo (EDL). Portanto, pode-se concluir que o T3 possui uma importante função na regulação da expressão de proteínas estruturais musculares e a ausência dessas proteínas pode ocasionar lesões das estruturas musculares cardíacas e esqueléticas. / Thyroid hormone (T3) regulates many functions of the heart and skeletal muscle. In this way, the present work identified the effect of T3 on the sarcomeric M band proteins, which are structural proteins from the heart and skeletal muscle. T3 down regulated M protein expression in the heart, one of the M band proteins, and, moreover, T3 could regulate M protein gene directly. In the skeletal muscle, T3 up regulated EH-myomesin expression in soleus muscle and T3 down regulated M protein expression in the extensor digitorum longus muscle (EDL). Therefore, we could conclude that T3 has an essential function in the regulation of muscle structural protein and the absence of these proteins could cause lesions at cardiac and skeletal muscle structures.

Diversos fatores respondem por variações na viabilidade do sêmen eqüino e na sua qualidade espermática; em humanos, reportam-se correlações entre fatores endócrinos e parâmetros seminais, mas em eqüinos poucos estudos contribuem para esta correlação. Para se investigar eventuais correlações entre hormônios sexuais e tireoideanos com as características seminais físicas e morfológicas, além de longevidade seminal, foram mensuradas as concentrações plasmáticas de estradiol, testosterona, T3 e T4 de garanhões e analisadas tais características espermáticas no momento da colheita seminal e após 24h, 48h e 72h de armazenamento a 5oC. 05 garanhões férteis em idade reprodutiva foram submetidos à colheita de sêmen (2 vezes/semana) e sangue (1 vez/semana, a cada 6 horas) durante 6 semanas. Estradiol, testosterona, T3 e T4 foram analisados por RIE. Após a colheita, o sêmen foi analisado e resfriado a 5oC, com análises subseqüentes após 24h, 48h e 72h de armazenamento. O sêmen foi avaliado quanto às características seminais físicas e morfológicas, além de integridade de membrana. Significativas (p<0.05) diferenças foram observadas entre os animais quanto às concentrações hormonais; o estradiol mostrou as maiores variações entre indivíduos, embora todos os resultados tenham se mostrado compatíveis aos valores de referência da literatura. Logo após a colheita, não se observou diferenças significativas (p<0.05) para vigor e motilidade total/progressiva, em exceção ao garanhão 4, que apresentou significativa menor motilidade progressiva inicial. Após 24h, 48h e 72h de resfriamento, diferenças significativas (p<0.05) foram observadas entre os garanhões; os menores índices de vigor/motilidade progressiva foram observados nos garanhões 1 e 4. Diferenças significativas (p<0.05) também foram observadas entre os animais para as características espermáticas morfológicas e integridade de membrana. Análises de covariância e correlações não demonstraram correspondência entre concentrações hormonais, longevidade espermática e características seminais físicas/morfológicas, tendo \"tempo de resfriamento\" e \"indivíduos\" como fatores. Correlação positiva foi observada entre motilidade progressiva/vigor e espermatozóides vivos com acrossomo intacto (r=0.70 e r=0.71 respectivamente); em analogia, correlação negativa foi encontrada entre motilidade progressiva/vigor e espermatozóides com acrossomo intacto (r=-0.70 e r=-0.72 respectivamente), indicando que, vivos ou mortos, apresentar acrossomo intacto é fator crítico para a viabilidade espermática mesmo após diferentes tempos de armazenamento em resfriamento. Os resultados mostram que a longevidade do sêmen eqüino provavelmente não é diretamente afetada por razões hormonais primárias; o mesmo pode ser considerado para morfologia espermática. Por outro lado, a longevidade do sêmen eqüino parece ser diretamente influenciada pela integridade de membrana espermática e eventualmente fatores bioquímicos, metabólicos e enzimáticos. / Several factors respond for variations of equine semen viability and sperm quality; in humans, scientific reports try to correlate endocrine issues and sperm parameters. In horses, few studies contribute to this correlation. In order to investigate eventual correlations between sexual and thyroid hormones with physical and morphologic characteristics and also longevity of equine semen,were measured plasma concentrations of estradiol, testosterone, T3 and T4 of stallions and analyzed physical and morphologic characteristics and membrane integrity of spermatozoa at the moment of collection and after 24, 48 and 72 hours of storage at 5oC. Five fertile stallions in reproductive age had semen (twice a week) and blood (once a week, every 6 hours) collected during 6 weeks. Estradiol, testosterone, T3 and T4 were analyzed by RIA. After collection, semen was analyzed and cooled at 5oC, with further analyses after 24, 48 and 72 hours of storage. Semen analysis consisted in physical, morphologic and embrane integrity characteristics. Significant (p<0.05) differences were observed among stallions when compared for plasma hormonal concentrations; estradiol showed the greater variations between individuals, despite all results were compatible to reference values in literature. Just after collection, no significant differences (p<0.05) were observed for vigor and total/progressive motility, in exception to stallion 4, that presented a significant lower initial progressive motility. After 24, 48 and 72 hours of storage, significant differences (p<0.05) were observed among stallions; lowest values of vigor/progressive motility were observed for stallions 1 and 4. Significant differences (p<0.05) were also observed among stallions for morphologic characteristics of sperm and membrane integrity. Analyses of covariance and correlations showed no correspondence among hormonal plasma concentrations, sperm longevity and physical/morphologic characteristics, having time of storage and individuals as factors. Meanwhile, a positive correlation was observed among progressive motility/vigor and live sperm with intact acrosome (r=0.70 and r=0.71 respectively); in analogy, a negative correlation was found among progressive motility/vigor and dead sperm with intact acrosome (r=-0.70 and r=-0.72 respectively), indicating that neither being live or dead, but having acrosome membrane intact is a critical factor for spermatozoa\'s viability even after different times of storage at cooling temperatures. Results show that longevity of equine semen is probably not directly affected by primary hormonal reasons; the same can be considered for sperm morphology. Otherwise, longevity of equine semen seems to be directly influenced by sperm membrane integrity and eventually by biochemical, metabolic and enzymatic factors.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 90-106).

The hypothalamic-pituitary-thyroid axis operates to maintain the circulating concentration of thyroid hormones. Thyrotropin releasing hormone (TRH) is the major hypothalamic messenger controlling the pituitary-thyroid unit. However, the pituitary-thyroid unit responses to various modalities of TRH exposure are not well characterized. Also, interactions between the thyroid axis and other mammalian organ systems, specifically other hormone axes, to maintain the organism's homeostatic state are not well characterized. This work was designed to clarify the response of the pituitary-thyroid unit to TRH and to assess the effects of physiological levels of the rat's primary adrenal cortical hormone, corticosterone, on the thyroid axis. Adult rats were given equal amounts of TRH by intravenous (I.V.) bolus injection or constant intraperitoneal (I.P.) infusion. Both methods resulted in significant increases in plasma thyroid stimulating hormone (TSH), although the time course and peak plasma value varied with the TRH dosage and administration method. Despite the differences in plasma TSH elicited, the thyroid gland responses were similar. Thus, the pituitary is sensitive to the rate and dose of TRH administration. Also, the thyroid is sensitive to plasma levels of TSH but reaches maximum stimulation at submaximal circulating TSH levels. Adrenalectomized female rats, with I.P. and I.V. catheters, were infused with corticosterone (B) to achieve plasma levels within the rat's physiological range. Plasma samples were drawn before and after submaximal TRH (250 ng/100 g Body Weight) administration for assay of TSH and B concentrations. B in the lower half of its physiological range significantly inhibited the increase in plasma TSH observed 10 and 30 minutes after TRH administration. Also, direct stereotaxic infusion of B (50 ng) followed by TRH (1 ng) into the anterior pituitary inhibited the observed increase in plasma TSH. These studies indicate that homeostatic thyroid axis hormone concentrations are maintained by a feedback loop mechanism which is modulated by adrenal hormones. Specifically, physiological levels of corticosterone decrease pituitary sensitivity to TRH in the rat. In addition, the pituitary and thyroid gland exhibit different response patterns to hormonal stimulation.

Biological factors regulating feed efficiency were investigated in replacement beef heifers to establish factors that differ between efficient and less efficient animals. Feed efficiency, measured as residual feed intake (RFI) adjusted for body ultrasound measurements, was determined in forty-seven cross-bred heifers. Reproductive differences between efficient (low RFI) and less efficient (high RFI) heifers were examined. Low RFI heifers had an earlier age at both sexual maturity (P=0.08) and conception (P=0.08), and delivered heavier calves (P=0.006). The potential of fecal progesterone metabolites (FP4M) as an indicator of sexual maturity was examined. Measurements of FP4M present a promising non-invasive alternative technique for determining the onset of sexual maturity. A subset of 36 heifers was used to determine if plasma triiodothyronine (T3) concentrations could be used to predict feed efficiency. Triiodothyronine concentrations a correlation of 0.58 (P=0.001) to those from a quadratic prediction model of RFI in heifers sampled as yearlings. / Research into reproductive characteristics associated with residual feed intake, and to determine the effectiveness of the thyroid hormones as a screening tool for feed efficient animals. / OMAFRA (Ontario Ministry of Agriculture, Food, and Rural Affairs) through the Farm Innovation Program, Agriculture Canada through the Growing Forward Project, the Canadian Cattlemen’s Association through the Beef Cattle Research Council, and the Ontario Cattlemen’s Association.

The ING (INhibitor of Growth) tumor suppressor genes are conserved from yeast to humans and are implicated in several processes important to cell proliferation and apoptosis. ING proteins contain a plant homeodomain (PHD) finger that suggests these proteins may modulate transcription factor-mediated pathways. Little is known about the mechanism of action of INGs, especially in the context of normal development. The ING family of proteins includes at least five different genes, ING1-ING5, with evidence for alternate promoter usage and splicing that generate multiple isoforms. To elucidate the role of ING in different tissues to modulate function, I used amphibian metamorphosis as a model system in which a single stimulus, thyroid hormone (TH), initiates apoptosis, proliferation, and remodeling in the tail, hindlimb, and brain, respectively. I discovered seven ING1 and three ING2 transcript variants in Xenopus laevis and investigated their expression patterns. High expression levels of most variants were found in adult brain, testis, and eye. During natural metamorphosis or precocious metamorphosis induced by treating tadpoles with exogenous TH, ING1 and ING2 transcript variant levels were differentially regulated in a tissue-specific manner. Some variant levels increased with the induction of apoptosis of the tail, while levels of the same variants decreased upon induction of proliferation and differentiation in the hindlimb. Although levels of all INC variants were relatively high in whole brain, they did not change during metamorphosis or TH treatment. Given that ING has previously been shown to modulate apoptosis, it is likely that upregulation of specific isoforms may contribute to the tissue-specific TH-mediated response in the tail, and that downregulation facilitates proliferation of the hindlimb. To further investigate the hypothesis that ING is regulated by TH, an analysis of 1NG1 and ING2 genomic sequences was carried out. Promoter sequences for each variant were determined and putative thyroid hormone response elements (TREs) located. To test whether thyroid hormone receptors associate with these elements, chromatin immunoprecipitations (ChIP) assays were done on tail homogenates from premetamorphic tadpoles treated with TH or vehicle control. Both thyroid hormone receptor α (TRα) and thyroid hormone receptor β (TRβ) differentially associate with ING1 and ING2 promoter regions. TR association increased significantly on promoters for ING variant transcripts that increase upon TH treatment, and decreased significantly on promoters for ING variant transcripts that decrease upon TH treatment. ChIPs also showed that ING associates with TH-regulated promoters including TRβ, TH-Responsive Basic Leucine Zipper Transcription Factor (TH/bZIP), ING1 and ING2. Furthermore, TR and ING were shown to co-immunoprecipitate with both purified proteins and using total tail homogenates from metamorphic tadpoles. The antibodies used for these experiments were made against Xenopus TRβ and ING2 and were characterized as part of this thesis. Bioinformatics revealed that TREs are present in promoters of ING genes for other species including human, mouse, and a related frog species, Xenopus tropicalis; therefore, it is likely that modulation by TH is a conserved mechanism of ING regulation. These data suggest that there may be antagonistic regulation of ING transcript variants by TH that correlates with tissue fate. TRs associate with ING promoters, and ING is associated with TR-regulated promoters. Moreover, TR and ING proteins co-immunoprecipitate. It is therefore likely that TR and ING are co-regulators of gene expression during TH-dependent tadpole metamorphosis. This thesis contributes to the understanding of ING which is relevant to elucidating many disease states, as well as being critical in understanding the role of this tumor suppressor in the context of TH regulation and normal development.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 3 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 4 uppsatser.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, 2007. / Kaynakça var.