Figure 2.

Mechanisms of action of DHEA and DHEAS in neurons. This cartoon summarizes many of the actions of DHEA and DHEAS described in detail in the text. DHEA and DHEAS have inhibitory effects (red blocking arrow) at the GABA_A receptor (section 6 and 7.1). DHEA and DHEAS act as agonists (green arrow) at the σ₁ receptor (section 6 and 7.1), which subsequently may activate the NMDA receptor. DHEA inhibits Ca²⁺ influx (red blocking arrow) into the mitochondria (section 7.1). DHEA influences embryonic neurite growth through stimulation (green arrow) of the NMDA receptor (section 7.2). DHEA increases (green arrow) kinase activity of Akt and decreases apoptosis, while DHEAS decreases (red blocking arrow) Akt and increases apoptosis (section 7.4). DHEAS increases (green arrows) TH mRNA and TH protein abundance (section 7.5) leading to increased catecholamine synthesis. DHEA and DHEAS stimulate (green arrows) actin depolymerization and submembrane actin filament disassembly and (green arrows), increasing secretion of catecholamines (“da” and “ne”) from secretory vesicles (section 7.5). DHEA and DHEAS inhibit (red blocking arrow) reactive oxygen species (ROS) activation of transcription mediated by NF-κB (section 7.6 and 7.7). DHEA inhibits (red blocking arrow) nuclear translocation of the glucocorticoid receptor (GR) (section 7.8). Mechanisms of action not pictured in this graph are: alterations of brain derived neurotrophic factor (BDNF) synthesis, inhibition of stress-activated protein kinase 3 (SAPK3) translocation, and inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSDl) activity. Abbreviations: σ₁, sigma 1 receptor; Akt, serine-threonine protein kinase Akt; Ca²⁺, calcium; da, dopamine; GABA_A, γ-aminobutyric acid type A receptor; GR, glucocorticoid receptor; ne, norepinephrine; NF-κB, nuclear factor kappa B; NMDA, N-methyl-D-aspartate receptor; ROS, reactive oxygen species; TH, tyrosine hydroxylase.