EVIDENCE FOR TARGET REGULATION OF THE DEVELOPMENT OF ANDROGEN SENSITIVITY IN RAT SPINAL MOTONEURONS

Specific neuronal circuits within the vertebrate nervous system expres s high levels of steroid receptors and are sensitive to the effects of steroid hormones, The mechanisms by which these neuronal circuits dev elop their unique steroid sensitivity are unknown. One intriguing hypo thesis is that retrograde influences during early postnatal life play a role in determining which central nervous system (CNS) neurons becam e sensitive to steroids. We now present evidence that during a critica l period in early postnatal development, axonal injury disrupts the no rmal development of steroid sensitivity. The spinal nucleus of the bul bocavernosus (SNB) is a neuromuscular system that is highly androgen-s ensitive at the level of both the motoneurons and their target muscles . Testosterone levels regulate the size of SNB motoneurons and their m uscles in adult rats. Cutting the axons of SNB motoneurons on postnata l day 14 (P14) caused permanent decreases in SNB motoneuronal soma siz e, as well as in SNB target muscle weight. Interestingly, SNB motoneur ons that survived axotomy on P14 failed to develop their normal abilit y to respond to testosterone in adulthood. That is, they did not respo nd to changes in testosterone levels with changes in soma size. The sa me effect was not seen after axotomy I week later in development, sugg esting a critical period for this effect. Thus, separation from the ta rget muscles during an early critical period in development blocked th e differentiation of androgen sensitivity by SNB motoneurons, consiste nt with a role for the target in the normal development of steroid sen sitivity by CNS neurons.