Nutritional and endocrine determinants of stress

The injured body manifests a cascade of cytokine-induced metabolic response s aiming at developing "defense mechanisms and tissue repair. Rising concen trations of counterregulatory hormones (cortisol, glucagon, catecholamines) and of growth hormone (GH) generate,a stage of insulin resistance in healt hy tissues, due to an acquired insulin post-receptor defect. The depression of both pituitary-thyroid axis and IGF-I production by the liver accounts for the slackening of energy and anabolic processes as the entire body econ omy is moving;towards lipid dependency. The liver and damaged tissues react along,pathways disconnected from central regulatory, systems, Cytokines pr omote the hepatic transcriptional synthesis of acute-phase reactants at the expense of acute-booster reactants, notably transthyretin (TTR), retinol b inding protein (RBP) and. transcortin (CBG). Working as pro hormonal reserv oirs, TTR and RBP release substantial amounts of thyroxine and of retinol i n the fi ee from, allowing the overstimulation of ligand-dependent processe s. The enzymatic cleavage of CBG and TBG by activated neutrophils, and that of the main carrier-protein (BP3) of IGF-I in the bloodstream allows peak endocrine and mitogenic influences at the site of inflammation. Energy supp ly of the injured territory is insured by glycolytic anaerobiosis. Healthy tissues and damaged territory thus manifest divergent patter ns of response to stressful agents. This adaptive dichotomy is strongly influenced by the preexisting nutritional status as assessed by TTR and REP blood values. Fo llowing the fi ce hormonal concept, the amplitude of thyro- and retinol-ind uced processes are determined by the fluxes of ligands released in free fro m, meaning proportionate to the decrement of their specific carrier-protein s. The review provides further insight into the molecular mechanisms whereb y malnourished patients with low TTR and REP blood concentrations display i nappropriate responses and incur the risk of higher mortality rates.