Acute 19-nortestosterone transiently suppresses hippocampal MAPK pathway and the phosphorylation of the NMDA receptor.
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 in vivo 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 in vivo effects of an anabolic androgenic steroid on two key elements in hippocampal synaptic plasticity.
Rossbach
Uwe L
UL
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, BMC, Box 591, S-751 24 Uppsala, Sweden.
Le Grevès
Madeleine
M
Nyberg
Fred
F
Zhou
Qin
Q
Le Grevès
Pierre
P
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D036388:Ephrin-B2 / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005485:Flutamide / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009277:Nandrolone / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism
D000726:Androgen Antagonists; D000728:Androgens; D036388:Ephrin-B2; D039561:Eukaryotic Initiation Factor-4E; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D009277:Nandrolone; D005485:Flutamide; D020928:Mitogen-Activated Protein Kinases