Spatial and temporal patterns of neurotrophic activities in rat adrenal medulla and cortex

We have studied the spatial distribution and temporal pattern of expression of neurotrophic factor (NTF) activity present in the rat adrenal gland. Tissue extracts of the densely innervated medulla and sparsely innervated cortex from adult and various developmental stages were assayed for their ability to promote the in vitro survival of embryonic chick ciliary (CG), dorsal root ganglia (DRG) and ventral spinal cord (SC) neurons. NTF activity was found in medulla but not in cortex extracts. NTF activity became first detectable at postnatal day (P) 12. At this developmental stage the cholinergic adrenomedullary innervation becomes functional. Specific activity successively increased in medulla extracts from P16 to P30 as revealed by the CG-assay. No further changes occurred during adulthood. In contrast, activity addressing SC neurons present in P16 and P30 medulla extracts could not be detected in adult stages P90 or P120. In DRG-assays, NTF activity could not be blocked by the addition of anti-NGF antibodies to medulla extracts. The activity was sensitive to heat and protease treatment suggesting its proteinaceous nature. At high concentrations cortex extracts had neurotoxic effects that were also seen when 10 microM of dexamethasone were added to saturated amounts of medulla extract. However, gel filtration of cortex material to remove low molecular components including corticosteroid hormones failed to reveal any NTF activity in these preparations. Adrenal NTF activity therefore appears to be restricted to the densely innervated medullary tissue. Moreover, our results also suggest a distinct temporal pattern of NTF activity in the adrenal gland.