The current review will address the problem of chronic stress, adaptation and maladaptation from the perspective of the HPA axis, perhaps the most thoroughly studied system linked to stress responses. The consequences of HPA axis activation are far-reaching, likely due to the ubiquity of glucocorticoid hormone receptors across multiple body compartments and the widespread impact of glucocorticoid hormones on gene expression. Glucocorticoid secretion is generally linked to stressful events. Consequently, glucocorticoids are often referred to as “stress hormones,” a designation that undermines appreciation of their primary functions, including redistribution of energy. Indeed, so-called “stress levels” of glucocorticoid secretion can even be observed at the peak of the circadian corticosteroid rhythm, representing a flux in hormone aimed at increasing energy supplies for the active, waking hours. With this caveat in mind, consistent activation of this system constitutes both a mechanism of stress adaptation and a potential challenge for the organism, the balance of which determines resistance or susceptibility to long-term pathologies.
