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.