Evidence for target regulation of the development of androgen sensitivity in rat spinal motoneurons.
Specific neuronal circuits within the vertebrate nervous system express high levels of steroid receptors and are sensitive to the effects of steroid hormones. The mechanisms by which these neuronal circuits develop their unique steroid sensitivity are unknown. One intriguing hypothesis is that retrograde influences during early postnatal life play a role in determining which central nervous system (CNS) neurons become sensitive to steroids. We now present evidence that during a critical period in early postnatal development, axonal injury disrupts the normal development of steroid sensitivity. The spinal nucleus of the bulbocavernosus (SNB) is a neuromuscular system that is highly androgen-sensitive at the level of both the motoneurons and their target muscles. Testosterone levels regulate the size of SNB motoneurons and their muscles in adult rats. Cutting the axons of SNB motoneurons on postnatal day 14 (P14) caused permanent decreases in SNB motoneuronal soma size, as well as in SNB target muscle weight. Interestingly, SNB motoneurons that survived axotomy on P14 failed to develop their normal ability to respond to testosterone in adulthood. That is, they did not respond to changes in testosterone levels with changes in soma size. The same effect was not seen after axotomy 1 week later in development, suggesting a critical period for this effect. Thus, separation from the target muscles during an early critical period in development blocked the differentiation of androgen sensitivity by SNB motoneurons, consistent with a role for the target in the normal development of steroid sensitivity by CNS neurons.
Lubischer
J L
JL
Program in Neuroscience, University of California, Los Angeles, USA.
Arnold
A P
AP
D000728:Androgens / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D013127:Spinal Nerves / Q000502:physiology; D013739:Testosterone / Q000378:metabolism / Q000502:physiology
D000728:Androgens; D013739:Testosterone