Role of steroid hormones in neuroendocrine adaptation to stress and pathophysiology of metabolic syndrome - molecular mechanisms and clinical implications

The metabolic syndrome is a cluster of metabolic disorders implying a high risk for type 2 diabetes and cardiovascular diseases. The objective of the proposed project is to understand the role of glucocorticoid and other steroid hormones in pathophysiology of the syndrome by elucidating multiple links between molecular mechanisms of these hormones action, the neuroendocrine response to stress or trauma and clinical manifestations of the syndrome. In order to integrate the generated knowledge, we will undertake a multidisciplinary study including molecular, cellular, endocrinological, biochemical, pharmacological, genetic and proteomic approaches. The study will be performed on animal models of the metabolic syndrome, on patients with the disorders related to the syndrome and in vitro, on human cells and tissues. In a series of carefully matched basic and clinical experiments, we will employ modern methodology and experimental approaches, from real-time PCR and semi quantitative Western blot to genetic analysis of gene variants and interaction proteomics. The findings of both basic and clinical studies are expected to be translated into the clinical practice and applied in the diagnosis and clinical management of the metabolic syndrome. The project outcome will be the result of a high level of communication and scientific exchange between the complementary academic and clinical competences of the three teams involved.