Endocrine Abstracts

Throughout evolution survival of humanity has relied on the ability to cope with stress, such as fasting, exercise, injury and inflammation. In general these conditions generate a metabolic stress response with release of stress hormones (adrenaline, glucagon, cortisol and growth hormone(GH)) and mobilisation of all major fuel sources - lipids, protein and carbohydrate. In addition bacterial ingredients (eg endotoxin/lipopolysaccharide (LPS)) and cytokines (TNF-alfa, interleukins) have independent metabolic effects including liberation of fat and protein from adipose tissue and muscle and induction of fever(‘exogenous and endogenous pyrogens’). The exact mechanisms triggering the release of stress hormones are uncertain. An increase in body temperature, whether induced by pyrogens (fever), exercise or heating with hot water, initiates hypersecretion of stress hormones, suggesting that the thermoregulatory unit in the preoptic part of hypothalamus is involved. The metabolic stress response may be divided into a rapid ‘fight-or-flight’ component, primarily driven by adrenaline and glucagon and a more slow component, driven by cortisol and GH, both being characterised by overall catabolism and increased levels of lactate and ketone body stress metabolites. Infusion studies have shown that: (i) adrenaline, cortisol and GH increase the release of fatty acids and induce insulin resistance (ii) glucagon and cortisol increase protein breakdown and urea formation (iii) all four hormones increase endogenous glucose production and (iv) GH preserves protein by decreasing protein breakdown and urea formation. To test the role of the pituitary gland during metabolic stress we have compared metabolic responses to LPS and TNF-alfa in hypopitutary and control subjects - these studies showed that HP patients had a much lesser increase in lipolysis, protein breakdown and urea formation and that intact pituitary function and appropriate cortisol and GH responses are crucial for a full metabolic stress response.