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Studies on the thermogenic effects of thyroidean hormones

Abstract

Through experimental approaches which include (i) recording of muscular electrical activity and well as muscle fiber typing by histochemistry and (ii) study of the expression of different genes through the measurement of the in vitro genic transcription, by run on assay, and the analysis and quantification of mRNAs by northern/dot blottings, primer extension and polimerase chain reaction, we propose to investigate the participation of the thyroidean hormones, particularly in the tissue transformation of T4 to T3, in the muscular facultative thermogenesis and in the brown adipose tissue, induced by the cold. In reality, these studies represent the continuation of the line of research of our laboratory which is centered on the understanding of the mechanisms involved in the thermogenic actions of thyroidean hormones. So far, we have shown that thyroidean hormones are capable of inducing important modifications in the composition of postural muscle fibers, making it so that the shivering set off by exposure to the cold results in a greater production of heat. In the same way, in brown adipose tissue, our studies focused on (i) the characterization of the T3 nuclear receptors in this tissue and the participation of the local desiodase in the occupation of these receptors in the different physiological situations, (ii) in the role of the thyroidean hormones and noradrenalin in the control of the expression of the mitochondrial decoupling protein, (ii) hormonal regulation of lipogenesis of brown adipose tissue. In the present proposal we contemplate the continuation of these studies aiming (i) to characterize the process of thermogenesis derived from shivering and the influence that thyroidean hormone shave on this process, aiming to construct a solid physiological base upon which, in the medium/long term, techniques of cellular/molecular biology may be applied, (ii) to characterize the intracellular signals generated by T3 and noradrenalin in brown adipose tissue which are involved with the induction of the expression of this gene, both at transcriptional level and in the increase of the half-life of its message observed after 24 hrs exposure to the cold, (iii) to study the participation of thyroidean hormones and catecholamines in the control of the expression of two genes which codify key enzymes for the lipogenic path, i.e. malic enzyme and acetyl-CoA-carboxilase. We believe that the carrying out of these experiments will bring important contributions to the relevant areas of physiology, e.g. thermoregulation and energy homeostasis, as well as cellular and molecular biology, e.g. intracellular hormonal signaling and regulation of genic expression. In addition to being important from many purely biological points of view, this new knowledge could have important implications for different medical problems such as obesity, fever, muscle dysfunction and thyroid gland. (AU)