Importantly, context plays a role in dictating how tissues respond to glucocorticoids. Equivalent levels of glucocorticoids can exert different effects on cellular function depending on stress history. For example, in hippocampus, the same dose of corticosterone down-regulates mTOR expression in chronically stressed animals, but not controls (Polman et al., 2012). mTOR is an important cell signaling pathway that is involved in neuroplasticity and subsequent control of mood (Li et al., 2010). Thus, the function of the mTOR pathway will be markedly different in the context of stress, which subsequently affects behavioral and physiological responses. These data suggest that glucocorticoids may have exaggerated impact when an organism is exposed to stress, even if absolute levels of hormone are not elevated to so-called “pathophysiologic” levels.
