We have previously demonstrated that systemic administration of testosterone differentially regulates the regenerative properties of injured hamster facial motor neurons, which are androgen receptor-containing cranial motor neurons. In this investigation, the hypothesis that testosterone alters the regenerative properties of rat sciatic motor neurons, which are androgen receptor-containing spinal motor neurons, was tested using fast axonal transport of radioactively labeled proteins to assess sciatic nerve regeneration. Adult castrated male rats were subjected to crush axotomy of the sciatic nerve at the level of the gemelli tendons (mid-thigh). One-half of the axotomized animals received subcutaneous implants of testosterone propionate (TP), with the remainder of the animals sham implanted with blank capsules. The outgrowth distances of the leading axons were measured at 5, 6, 7, and 11 days postoperative. Linear regression analysis was accomplished, with the slope of the line representing the regeneration rate and the x-intercept the initial delay of sprout formation. Systemic administration of testosterone resulted in a 13% increase in the rate of regeneration, relative to the control, -TP group. Outgrowth distances were significantly increased in the +TP group only in the later stages of regeneration. However, TP did not shorten the delay in sprout formation in regenerating sciatic motor neurons, but instead produced a small prolongation in the delay time. This pattern of hormonal regulation of the regenerative properties of spinal motoneurons is similar to that previously found in cranial motoneurons. The prolongation of the initial delay may have been a factor in the lack of significant outgrowth distances during the early stages of regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

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Following injury of sciatic motor axons in the rat, the rate of axonal outgrowth is faster if there has been a prior "conditioning" axotomy. The acceleration of outgrowth is due to an acceleration of SCb, the rate [slow (SC)] component of axonal transport that carries cytomatrix proteins; this occurs throughout the axon by 7 days after the conditioning axotomy (Jacob and McQuarrie, 1991a, J. Neurobiol. 22:570-583). To further characterize the conditioning lesion effect (CLE), it is important to know (1) the minimum effective conditioning interval (time between conditioning and testing lesions), (2) whether the cell body reaction is required, and (3) whether outgrowth accelerates after a single axotomy. Outgrowth distances were measured by radiolabeling all newly synthesized neuronal proteins and detecting those carried to growth cones by fast axonal transport. When the conditioning and testing lesions were made simultaneously (0 day conditioning interval), there was no CLE. With a conditioning interval of 3 days, there was a shortening of the initial delay (before the onset of outgrowth) without a change in outgrowth rate. With conditioning intervals of 7, 14, and 21 days, the rates of outgrowth were increased by 8%, 22%, and 11%, respectively. To determine whether the cell body reaction to axotomy is necessary for the CLE, a nonaxotomizing stimulus to axonal growth (partial denervation) was used in place of a conditioning axotomy. This had no effect on the rate of outgrowth from a testing lesion made 14 days later. Finally, we examined the possibility that outgrowth accelerates after a single lesion. Outgrowth was faster at 6-9 days after axotomy than at 3-6 days (p < 0.001), and accelerated further at 9-12 days (p < 0.001). We conclude that (1) the shortest effective conditioning interval is 3 days; (2) the cell body reaction is necessary for the CLE; (3) axonal outgrowth from a single axotomy accelerates in concert with the anabolic phase of the cell body reaction. The SCb motor is, in turn, upregulated by this reaction. This suggests that the SCb motor responds to a fast-transported signal that is a product of the cell body reaction.

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