Acute 19-nortestosterone transiently suppresses hippocampal MAPK pathway and the phosphorylation of the NMDA receptor

Uwe L. Rossbach (1) , Madeleine Le Grevès (2) , Fred Nyberg (1) , Qin Zhou (1) , Pierre Le Grevès (3)

1 Division of Biological Research on Drug Dependence
2 Department of Neuroscience
3 Division of Neurobiology

High doses of anabolic androgenic steroid are associated with changes in personality, e.g. increased aggression and irritability, behavioural changes that may be linked to structural changes in the hippocampus. In this study we demonstrate acute effects of a single injection of 19-nortestosterone on proteins that play a major role in molecular plasticity at synaptic connections. The steroid rapidly and transiently decreased total and phosphorylated NMDA receptor GluN2B subunit levels and phosphorylated extracellular signal-regulated kinase 1 in rat hippocampal synaptoneurosomes. Pretreatment with the androgen receptor antagonist flutamide prevented these effects suggesting an androgen receptor mediated mode of action. However, flutamide alone stimulated the phosphorylation of both extracellular signal-regulated kinase 1 and 2. EphrinB2 and phosphorylated translation initiation factor 4E, two proteins that act on synaptic plasticity through NMDA receptor and/or mitogen-activated protein kinase pathways, were not affected by any of the treatment regimens. This study demonstrates rapid effects of an anabolic androgenic steroid on two key elements in hippocampal synaptic plasticity.

Mots clés: Anabolic androgenic steroids; phosphorylation; ERK; NMDA receptor; hippocampus; synaptoneurosomes

Uwe L. Rossbach, Madeleine Le Grevès, Fred Nyberg, Qin Zhou, Pierre Le Grevès. Acute 19-nortestosterone transiently suppresses hippocampal MAPK pathway and the phosphorylation of the NMDA receptor. Molecular and Cellular Endocrinology, 2009, 314 (1), pp.143. ⟨10.1016/j.mce.2009.07.027⟩. ⟨hal-00529005⟩