Orphan nuclear receptors: Shifting endocrinology into reverse

Steroid and thyroid hormones and vitamin A metabolites (retinoids) regulate the expression of complex gene programs by binding to members of the nucle ar receptor family of Ligand-activated transcription factors. The nuclear r eceptor family also includes many "orphan" members that currently lack know n Ligands but that represent candidate receptors for new hormones. Recently , natural and synthetic Ligands have been identified for several orphan rec eptors and used to dissect their biological roles. This "reverse endocrinol ogy" strategy has resulted in the discovery of unanticipated nuclear signal ing pathways for retinoids, fatty acids, eicosanoids, and steroids with imp ortant physiological and pharmacological ramifications.