title: Molecular dynamics of ultradian glucocorticoid receptor action.
abstract: In recent years it has become evident that glucocorticoid receptor (GR) action in the nucleus is highly dynamic, characterized by a rapid exchange at the chromatin template. This stochastic mode of GR action couples perfectly with a deterministic pulsatile availability of endogenous ligand in vivo. The endogenous glucocorticoid hormone (cortisol in man and corticosterone in rodent) is secreted from the adrenal gland with an ultradian rhythm made up of pulses at approximately hourly intervals. These two components - the rapidly fluctuating ligand and the rapidly exchanging receptor - appear to have evolved to establish and maintain a system that is exquisitely responsive to the physiological demands of the organism. In this review, we discuss recent and innovative work that questions the idea of steady state, static hormone receptor responses, and replaces them with new concepts of stochastic mechanisms and oscillatory activity essential for optimal function in molecular and cellular systems.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, UK. b.conway-campbell@bristol.ac.uk
authors.forename: Becky L
authors.initials: BL
authors.lastname: Conway-Campbell
authors.forename: John R
authors.initials: JR
authors.lastname: Pooley
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Hager
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
mesh_terms: D000204:Activity Cycles; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D021381:Protein Transport; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid