Anabolic steroids prevent disuse atrophy and reverse atrophy caused by glucocorticoids. To determine whether these beneficial effects extend to denervation atrophy, we tested whether nandrolone blocked denervation atrophy acutely or reversed subacute denervation atrophy. We also tested the association of such anabolic effects with expression of MAFbx, MuRF1 (both of which accelerate denervation atrophy), and IGF-1 (which prevents such atrophy). When begun at the time of denervation, nandrolone did not alter atrophy or expression of MAFbx, MuRF1, or IGF-1 measured 3, 7, or 14 days thereafter. When nandrolone administration was begun 28 days after denervation, atrophy was significantly reduced 7 and 28 days later (16% and 30%, respectively), and this was associated with significant reductions in expression of MAFbx and MuRF1, without alterations in the expression of IGF-1. The findings indicate that the actions of nandrolone depend on time after nerve transection and that the timing of anabolic steroid administration is an important determinant of responses of atrophying muscle to these agents.

Causes of disuse atrophy include loss of upper motor neurons, which occurs in spinal cord injury (SCI) or lower motor neurons (denervation). Whereas denervation quickly results in muscle fibrillations, SCI causes delayed onset of muscle spasticity. To compare the influence of denervation or SCI on muscle atrophy and atrophy-related gene expression, male rats had transection of either the spinal cord or sciatic nerve and were sacrificed 3, 7, or 14 days later. Rates of atrophy increased gradually over the first week after denervation and then were constant. In contrast, atrophy after SCI peaked at 1 week, then declined sharply. The greater atrophy after SCI compared to denervation was preceded by high levels of ubiquitin ligase genes, MAFbx and MuRF1, which then also markedly declined. After denervation, however, expression of these genes remained elevated at lower levels throughout the 2-week time course. Interestingly, expression of the muscle growth factor, IGF-1 was increased at 3 days after denervation when fibrillation also peaks compared to SCI. Expression of IGF-1R, GADD45, myogenin, and Runx1 were also initially increased after denervation or SCI, with later declines in expression levels which correlated less well with rates of atrophy. Thus, there were significant time-dependent differences in muscle atrophy and MAFbx, MuRF1, and IGF-1 expression following SCI or denervation which may result from distinct temporal patterns of spontaneous muscle contractile activity due to injury to upper versus lower motor neurons.