Novel mechanisms for DHEA action

J Mol Endocrinol. 2016 Apr;56(3):R139-55. doi: 10.1530/JME-16-0013. Epub 2016 Feb 23.

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.

Keywords: DHEA; DHEA-S; G-protein-coupled receptors; nuclear receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System / metabolism
  • Dehydroepiandrosterone / biosynthesis
  • Dehydroepiandrosterone / metabolism*
  • Gene Expression Regulation
  • Humans
  • Metabolic Networks and Pathways
  • MicroRNAs / genetics
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Neurons / metabolism
  • Organ Specificity
  • Peroxisome Proliferator-Activated Receptors / chemistry
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Steroid / chemistry
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism
  • Signal Transduction

Substances

  • MicroRNAs
  • Peroxisome Proliferator-Activated Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • constitutive androstane receptor
  • Dehydroepiandrosterone