Abstract

Activation of the hypothalamic-pituitary-adrenal (HPA) axis and altered tissue glucocorticoid action in obesity, metabolic syndrome and hypertension has been attributed to altered peripheral cortisol metabolism. Our work investigates the role of glucocorticoid metabolism, transport and receptor activation in horses, humans and mice and the impact of glucocorticoid metabolism on health and disease. We have identified novel pathways of cortisol metabolism in the horse associated with disease and have gone on to look at these pathways in humans and in animal models of disease. We focus on predominant cortisol metabolite in horses, 20β-dihydrocortisol which we have shown to be a preferential agonist of the mineralocorticoid receptor and our current work aims to elucidate the role of this metabolism in obesity associated hypertension in different species.