Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids.

Glucocorticoids play an essential role in maintaining basal and stress-related homeostasis, and lack of glucocorticoid action is incompatible with life in primates. Most known effects of glucocorticoids are mediated by the intracellular GR. The magnitude of a cell's response to glucocorticoids depends both on the hormone level it is exposed to and on its glucocorticoid sensitivity, i.e. the efficiency of GR-mediated signal transduction. In this review, we have summarized the multiple endogenous and exogenous factors that have been shown to be involved in this signaling cascade and, thus, to alter glucocorticoid sensitivity.