Dehydroepiandrosterone sulfate and dehydroepiandrosterone: neuroactive neurosteroids

Abstract

During the last five years, advances have been made in understanding of the role of dehydroepiandrosterone sulfate (DHEAS) and dehydroepiandrosterone (DHEA) in the central nervous system (CNS). It has become clear that the two molecules can be qualified as neurosteroids and neuroactive steroids. Sensitive procedures using gas chromatography-mass spectrometry are now available for simultaneous quantitation of several neurosteroids in small regions of the CNS in individual animals. Recent positive data about DHEA and DHEAS biosynthesis in the rat brain have been obtained and new metabolic pathways have been defined. Increasing evidence supports that there are neuromodulatory functions of DHEA and DHEAS in the CNS, including the modulation of neurotransmission, behavior, and neurotrophicity. The increased understanding of the mechanisms underlying DHEAS-induced enhancement of brain excitability is related to a refined analysis of synaptic transmission parameters and the use of enantiomer analogs for interaction with neurotransmitter receptors. Advances are being made in the research of the effects of DHEAS on cognition through use of sulfatase inhibitors that may reveal the physiological role of DHEA and DHEAS in memory. In humans, the profound age-related decrease of DHEA and DHEAS in the blood level is postulated to be associated with impairment of health. DHEA supplementation may help maintain a number of physiological functions, but scientists are aware of the need to conduct better-controlled clinical trials before definitive statements can be made.