DHEA and DHEA-S, and their functions in the brain and adrenal medulla

Abstract

Produced by the adrenal glands and the brain, neuroactive steroids dehydroepiandrosterone and its sulfate ester - DHEA and DHEA-S - are the most abundant hormones in the human body. DHEA and DHEA-S are known to exert major physiological and pathological effects on cognitive functions and memory. Interestingly, DHEA and DHEA-S levels gradually decline during aging; this decrease has been associated with neuronal degeneration processes and dysfunction. Moreover, DHEA has recently been identified as a regulator in neuronal stem cell proliferation. In animal models, DHEA has shown protective properties against a variety of diseases including obesity, diabetes, immune disorders, atherosclerosis and cancer. There is some evidence of the beneficial effects of DHEA in patients with adrenal insufficiency. However, the exact effects of DHEA and DHEA-S on brain and adrenomedullary function and the signaling pathways mediating these effects are not fully understood. Recent studies have provided evidence that DHEA can act via G- protein-associated, membrane-bound receptors, and that DHEA acts as a gamma-aminobutyric acid type A (GABAA) antagonist. Moreover, these steroids are able to potentiate glutamate action in neuronal cells. Additional studies are needed to develop a more complete picture of DHEA and DHEA-S functions in human physiology and pathology. © 2008 Springer Netherlands.