Glucocorticoids (GCs) are steroid hormones that regulate the physiology of all tissues and mediate stress responses. Synthetic GCs are commonly prescribed to treat chronic inflammatory conditions including the prevalent skin diseases—psoriasis and atopic dermatitis. GCs act through the GC receptor (GR, NR3C1), a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. In skin, GC therapeutic efficacy is due to the antiproliferative and anti-inflammatory actions of GR; however, in the long term, these benefits are accompanied by adverse profiles including skin atrophy, increased fragility, dehydration, augmented susceptibility to infections, and delayed wound healing. While the therapeutic actions of GC treatments have been extensively studied, only more recently has the physiological role of GR been addressed in skin. In vivo and in vitro studies in mouse and man have revealed an important function for GR in skin homeostasis. In particular, the characterization of gain- or loss-of-function mouse models has demonstrated relevant roles for GR in skin pathophysiology. The actions of GR are context dependent, and in skin, it regulates different gene subsets and biological processes depending on developmental stage and physiological state. Finally, recent findings emphasize the relevance of local GC biosynthesis and appropriate GR expression in maintaining skin homeostasis.
Part of the book: Keratin