Interaction of BDNF and testosterone in the regulation of adult perineal motoneurons.
In androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB), we investigated the interaction of BDNF (brain-derived neurotrophic factor) and testosterone to understand whether each factor gates the ability of the other to regulate androgen receptor expression and soma size, and whether each factor requires the presence of the other for its action. We axotomized SNB motoneurons and applied BDNF or PBS (phosphate-buffered saline) to the cut ends of the axons in rats that were castrated and treated with either testosterone or placebo. Control groups were either not castrated or not axotomized, or had intact SNB axons and were castrated and treated with testosterone or placebo. We found that testosterone determined the expression of nuclear androgen receptor, and this effect was enhanced by both BDNF and contact with the target muscles. The effect of BDNF on androgen receptor expression was seen only when testosterone was present. In the regulation of soma size, BDNF dominated. The application of BDNF completely compensated for the loss of testosterone in castrated males so that the testosterone effect on soma size was seen only in intact SNB motoneurons and in axotomized motoneurons treated with PBS. Moreover, testosterone increased androgen receptor and soma size in axotomized SNB motoneurons, indicating that testosterone can act on sites other than the target muscles of the SNB to regulate each of these. These results indicate that the regulation of androgen receptor by testosterone does not require BDNF, but the regulation of androgen receptor by BDNF does require testosterone. The regulation of soma size by BDNF does not require high expression of nuclear androgen receptor.
Yang
L Y
LY
Department of Physiological Science, 621 Charles E. Young Drive South, University of California, Los Angeles, California 90095-1527, USA. yangly@ucla.edu
Arnold
A P
AP
D000818:Animals; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000502:physiology; D002369:Castration; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D013739:Testosterone