Novel mechanisms for DHEA action
- Department of Biochemistry and Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, USA
- Correspondence should be addressed to C M Klinge; Email: carolyn.klinge{at}louisville.edu
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.
- Received 22 February 2016
- Accepted 23 February 2016
- Made available online as an Accepted Preprint 1 April 2016
- © 2016 Society for Endocrinology
