Mechanisms of exercise-induced alterations in the hypothalamo-pituitary adrenal axis activity

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Glucocorticoids are naturally occurring hormones that have several functions within the body, which include control of blood sugar levels, mobilization of fat and protein stores and immune suppression. During periods of stress, the Hypothalamo-Pituitary-Adrenal (HPA) axis releases high levels of glucocorticoids that prepare the organism for defence. Chronic elevations in glucocorticoids are undesirable, however, and appear to be linked to a number of immune, growth, neurological and metabolic disorders. As such, glucocorticoids must be tightly regulated within the body via specific glucocorticoid receptors in the brain and pituitary gland (i.e. negative feedback) and by enzymes in the various target tissues (e.g. fat, muscle and liver) that can either activate or inactivate local glucocorticoids. Poor regulation of glucocorticoids and chronic elevations in HPA activity are thought to be critical in the development of a common clinical condition called the Metabolic Syndrome (insulin resistance, high blood glucose, central obesity and high blood pressure), although the exact mechanism for this is unclear. Paradoxically, regular exercise, which is a potent activator of the HPA activity, is beneficial in preventing or improving many of these metabolic disorders. My laboratory is interested in determining if regular exercise (i.e. training) influences: 1) basal HPA activity; 2) HPA feedback sensitivity and; 3) local glucocorticoid activation. Moreover, we are particularly interested if some of the preventative effects of regular exercise on the development of the Metabolic Syndrome are via alterations in the HPA axis. We have recently shown that short term exercise behaviour increases resting HPA activity, while long term training causes a reduction in basal activity in healthy rodents. These adaptations appear to be mediated by changes in the gene expression of key regulatory proteins in the brain and pituitary gland as well as by changing the adrenal gland sensitivity to produce glucocorticoids. We are now interested in elucidating the molecular mechanisms for central and peripheral HPA adaptation to training and to explore the links between exercise, HPA activity and disease prevention.