Hypothalamic regulation of metabolism Role of thyroid hormone and estrogen

Thyroid hormone and estrogen both play an essential role in energy metabolism. The current thesis investigated the possible central effects of these hormones in the control of energy metabolism by administrating triiodothyronine (T3), estradiol (E2) and thyrotropin-releasing hormone (TRH) in distinct hypothalamic nuclei. We evaluated various aspects of metabolic alterations including glucose and lipid metabolism, food intake, body weight, body temperature, locomotor activity, energy expenditure and bone remodelling, from gene expression to behavioural changes. For these experiments, we used different experimental techniques. For example, we used slow-releasing pellets for chronic T3 or E2 administration and microdialysis for acute TRH or E2 administration into hypothalamus. We used metabolic cages to monitor caloric parameters including energy expenditure, carbohydrate oxidation and locomotor activity. We used positron emission tomography (PET) and micro computed tomography (μ-CT) scans to examine brown adipose tissue (BAT) activation and bone morphology, respectively. A number of different surgeries have been applied such as ovariectomy, liver denervation, brain cannulation and jugular vein catheterization, to help explicating specific research questions. Our results suggest an essential role of hypothalamus in the estrogenic regulation of fat and bone metabolism as well as in the TRH regulation of glucose and body temperature. Our T3 experiments also suggest that the timing and route of central T3 administration may be important determinants of metabolic effect size. We believe these new findings not only extend our physiological understanding of hypothalamic regulation of metabolism, but also indicate potential therapeutic possibilities for metabolic diseases.