The effect of dehydroepiandrosterone sulfate and allopregnanolone sulfate on the binding of [3H]ifenprodil to the N-methyl-d-aspartate receptor in rat frontal cortex membrane

Allopregnanolone induces LHRH and glutamate release through NMDA receptor modulation

“…It has been demonstrated that some sulfated neurosteroids modulate NMDA receptor activity via a steroid modulatory domain on the NMDA receptor NR2B subunit [18,28]. The results suggest that the non sulfated neurosteroid allopregnanolone could interact with NMDA receptors modulating the release of LHRH.…”

“…However, interaction of allopregnanolone with other neurotransmitter receptors, like glutamate receptors, has not been greatly studied. Other neurosteroids have been shown to interact with glutamatergic NMDA receptors activity such as pregnanolone sulfate [17], dehydroepiandrosterone sulfate, and allopregnanolone sulfate [18]. However, non sulfated neurosteroids like allopregnanolone have not been demonstrated to interact with NMDA receptors.…”

Neurosteroids alter glutamate-induced changes in neurite morphology of NG108-15 cells

“…We recently demonstrated an interaction between neurosteroids and the binding site for the NMDA receptor antagonist ifenprodil, which is also located on the NR2B subunit [7,8]. Of the tested neurosteroids, PS and 3␣5␤S induced distinct effects on [ 3 H]ifenprodil binding kinetics, which had characteristics indicative of allosteric interactions with the NMDA receptor.…”

Effect of gonadal hormones and neurosteroids on injury-induced microglia and astroglia activation

“…DHEA may also exert its effect via conversion to estradiol or to sulfated or hydroxylated metabolites. Its sulfated form (DHEAS) can modulate NMDA (Johansson and Le Greves 2005) and sigma 1 receptors (Zou et al 2000). Furthermore, its 7alpha-and 7beta-hydroxylated metabolites may also play a role in its action (Jellinck et al 2001;Jellinck et al 2005).…”

“…When analyzing the mode of action of DHEA, there are several possibilities that have to be taken into account, such as acting through conversion into androgens and/or estrogens (Akwa et al 1991;Zwain and Yen 1999), and acting directly on GABA receptor type A (Perez-Neri et al 2008) or through its sulfated form on NMDA or sigma 1 receptors (Zou et al 2000;Johansson and Le Greves 2005). Little is known, however, on the mechanisms of action when it comes to newly synthesized DHEA derivatives.…”