Is There a Receptor for Dehydroepiandrosterone or Dehydroepiandrosterone Sulfate?

Abstract

It remains unknown whether dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) have a physiological role other than serving as metabolic intermediates in androgen synthesis. Apart from intracellular metabolism, there is no convincing cellular mechanism of action for physiological concentrations of DHEA(S). Unlike other major steroids, a receptor for DHEA(S) has not been definitively isolated. This article will review the evidence supporting a receptor-dependent basis for the direct physiological effects of DHEA(S). The data supporting an intracellular receptor for DHEA(S) are relatively weak and do not allow us to determine whether DHEA(S) directly, or a metabolite of DHEA(S), acts as a direct receptor ligand. Recent data strongly support a plasma membrane receptor for DHEA, but this potential receptor is yet to be isolated. Definitive characterization of the molecular mechanism (receptor or otherwise) of DHEA(S) action is necessary before we can determine whether DHEA(S) has a biological role other than as an androgen precursor.