In vitro activity: Dehydroepiandrosterone reversibly blocks GABA-induced currents, behaving as an allosteric antagonist of the GABAA receptor in cultured neurons from ventral mesencephalon. Dehydroepiandrosterone (DHEA) protects primary hippocampal cultures from embryonic day 18 (E18) embryos against NMDA-induced toxicity, DHEAS also reduces NMDA-induced toxicity. DHEA (100 nM) protects cultured neurons against the neurotoxic actions of either AMPA (25 mM) or kainic acid (1 mM) as well. Dehydroepiandrosterone (DHEA) increases the length of neurites containing the axonal marker Tau-1 in primary cultures of mouse embryonic neocortical neurons, and the incidence of varicosities and basket-like process formations in a dose-dependent fashion. Dehydroepiandrosterone (DHEA) rapidly increases free intracellular calcium via activation of N-methyl-D-aspartate (NMDA) receptors. Dehydroepiandrosterone with H874Y stimulates a 3- to 8-fold greater response than with wild type AR and at 100 nM the response is similar with the LNCaP mutant in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells.

Cell Assay: Treatment of T. crassiceps with DHEA decreasd reproduction, motility and viability in a dose- and time-dependent fashion. Moreover, Pre-treatment with DHEA (10–100 nM for 6–8 h) protected hippocampal neurons against excitatory amino acid (0.1, 1, 10, and 50 mM)-induced neurotoxicity in vitro.

Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1852-7; Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4678-83.