Evidence that androgen acts through NMDA receptors to affect motoneurons in the rat spinal nucleus of the bulbocavernosus.
In adult male rats, spinal nucleus of the bulbocavernosus (SNB) motoneurons shrink after castration and are restored in size after androgen treatment. Sixty-day-old Sprague Dawley males were castrated and implanted with SILASTIC capsules containing testosterone (T) or nothing, and osmotic minipumps continuously infusing MK-801, a noncompetitive NMDA receptor antagonist, or saline. Twenty-five days later, bulbocavernosus muscles were injected with the retrograde tracer cholera toxin-horseradish peroxidase conjugate (CT-HRP) to label SNB cells. As seen previously, among saline-treated rats, SNB somata of T-treated castrates were significantly larger than those of castrates receiving blank capsules (p < 0.0001). MK-801 treatment blocked this effect of T on the SNB. MK-801 had no effect on non-androgen-responsive spinal motoneurons in the neighboring retrodorsolateral nucleus (RDLN), nor did the drug affect SNB soma size in the absence of androgen treatment. Motoneuronal soma size in Nissl stain revealed the same pattern of results seen with CT-HRP fills. In situ hybridization indicated that SNB motoneurons express mRNA for the NMDA receptor subunits R1, R2a, and R2b. Castration reduced the expression of R1 mRNA in SNB motoneurons, an effect that was blocked by androgen replacement in castrates. R2A and R2B mRNA expression in SNB cells was not affected by androgen manipulations. Likewise, androgen manipulations had no effect on the expression of any NMDA receptor subtypes in RDLN motoneurons. These results suggest that androgen affects the size of SNB motoneurons by influencing their expression of the NMDA receptor, and therefore the response of the motoneurons to endogenous glutamate.
Jordan
Cynthia L
CL
Neuroscience Program and Psychology Department, Michigan State University, East Lansing, Michigan 48824, USA.
Christensen
Scott E
SE
Handa
Robert J
RJ
Anderson
Jennifer L
JL
Pouliot
Wendy A
WA
Breedlove
S Marc
SM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002369:Castration; D048429:Cell Size / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D020249:Hormone Replacement Therapy; D017403:In Situ Hybridization; D015918:Infusion Pumps, Implantable; D008161:Lumbosacral Region; D008297:Male; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012669:Seminal Vesicles / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000008:administration & dosage / Q000037:antagonists & inhibitors
D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists; D021122:Protein Subunits; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013739:Testosterone; D016291:Dizocilpine Maleate