[Beyond glucocorticoids, retinoids and vitamin D--the evolution of nuclear hormone type transcription factor...

Nuclear hormone receptors are ligand-dependent transcription factors. The class of nuclear hormone receptors that form heterodimers with retinoid X receptor includes members that are well established targets of current dermatological therapeutics such as the retinoic acid receptor (RAR) and the vitamin D receptor (VDR) as well as more recently discovered receptors including the peroxisome proliferator-activated receptors (PPAR) and the liver X receptor (LXR). After ligand activation (often lipid metabolites), these intracellular receptors exert their functions by binding to specific response elements in regulatory sequences of target genes, preferentially those involved in differentiation, energy expenditure and lipid metabolism. A number of selective activators has been developed by combinational chemistry, initially for their anti-diabetic and lipid lowering properties as well as their ability to regulate bile acid and drug metabolism. However, these activators also have marked effects on cutaneous homeostasis. Therefore, these compounds have important implications for dermatological therapy. In this review, the clinical implications of the more recently discovered members of the nuclear hormone receptor family are discussed.