title: Orphan nuclear receptors: shifting endocrinology into reverse.
abstract: Steroid and thyroid hormones and vitamin A metabolites (retinoids) regulate the expression of complex gene programs by binding to members of the nuclear receptor family of ligand-activated transcription factors. The nuclear receptor family also includes many "orphan" members that currently lack known ligands but that represent candidate receptors for new hormones. Recently, natural and synthetic ligands have been identified for several orphan receptors and used to dissect their biological roles. This "reverse endocrinology" strategy has resulted in the discovery of unanticipated nuclear signaling pathways for retinoids, fatty acids, eicosanoids, and steroids with important physiological and pharmacological ramifications.
authors.affiliation: Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Five Moore Drive, Research Triangle Park, NC 27709, USA. sak15922@glaxowellcome.com
authors.forename: S A
authors.initials: SA
authors.lastname: Kliewer
authors.forename: J M
authors.initials: JM
authors.lastname: Lehmann
authors.forename: T M
authors.initials: TM
authors.lastname: Willson
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D006728:Hormones / Q000502:physiology; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D011956:Receptors, Cell Surface / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D004268:DNA-Binding Proteins; D006728:Hormones; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated