Androgens rescue avian embryonic lumbar spinal motoneurons from injury-induced but not naturally occurring cell death

The regulation of survival of spinal motoneurons (MNs) has been shown to de pend during development and after injury on a variety of neurotrophic molec ules produced by skeletal muscle target tissue. Increasing evidence also su ggests that other sources of trophic support prevent MNs from undergoing na turally occurring or injury-induced death. We have examined the role of end ogenous and exogenous androgens on the survival of developing avian lumbar spinal MNs during their period of programmed cell death (PCD) between embry onic day (E)6 and E11 or after axotomy on E12, We found that although treat ment with testosterone, dihydrotestosterone (DHT), or the androgen receptor antagonist flutamide (FL) failed to affect the number of these MNs during PCD, administration of DHT from E12 to E15 following axotomy on E12 signifi cantly attenuated injury-induced MN death. This effect was inhibited by cot reatment with FL, whereas treatment with FL alone did not affect MN surviva l. Finally, we examined the spinal cord at various times during development and following axotomy on E12 for the expression of androgen receptor using the polyclonal PG-21 antibody. Our results suggest that exogenously applie d androgens are capable of rescuing MNs from injury-induced cell death and that they act directly on these cells via an androgen receptor-mediated mec hanism. By contrast, endogenous androgens do not appear to be involved in t he regulation of normal PCD of developing avian MNs. (C) 1999 John Wiley & Sons, Inc.