title: Novel mechanisms for DHEA action.
abstract: Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA), secreted by the adrenal cortex, gastrointestinal tract, gonads, and brain, and its sulfated metabolite DHEA-S are the most abundant endogeneous circulating steroid hormones. DHEA actions are classically associated with age-related changes in cardiovascular tissues, female fertility, metabolism, and neuronal/CNS functions. Early work on DHEA action focused on the metabolism to more potent sex hormones, testosterone and estradiol, and the subsequent effect on the activation of the androgen and estrogen steroid receptors. However, it is now clear that DHEA and DHEA-S act directly as ligands for many hepatic nuclear receptors and G-protein-coupled receptors. In addition, it can function to mediate acute cell signaling pathways. This review summarizes the molecular mechanisms by which DHEA acts in cells and animal models with a focus on the 'novel' and physiological modes of DHEA action.
authors.affiliation: Department of Biochemistry and Molecular GeneticsCenter for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Prough
authors.affiliation: Department of Biochemistry and Molecular GeneticsCenter for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Clark
authors.affiliation: Department of Biochemistry and Molecular GeneticsCenter for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, USA carolyn.klinge@louisville.edu.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Klinge
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D000090702:Constitutive Androstane Receptor; D003687:Dehydroepiandrosterone / Q000096:biosynthesis / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D053858:Metabolic Networks and Pathways; D035683:MicroRNAs / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D047492:Peroxisome Proliferator-Activated Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000090702:Constitutive Androstane Receptor; D035683:MicroRNAs; D047492:Peroxisome Proliferator-Activated Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D003687:Dehydroepiandrosterone
keywords: DHEA; DHEA-S; G-protein-coupled receptors; nuclear receptors