Axons Containing the Growth Associated Protein GAP‐43 Specifically Target Rat Corticotrophs Following Adrenalectomy

An extensive network of nerve fibers immunoreactive for the neuronal growth associated protein GAP‐43 (GAP‐43‐IR) is present within the anterior pituitary (AP) of the rat, and the density of these fibers has been reported to increase 4 days after adrenalectomy (ADX). In the present study, we employed confocal dual‐label immunofluorescence microscopy to determine whether GAP‐43‐IR fibers are specifically associated with corticotrophs at various intervals after ADX. A dramatic increase in the density of GAP‐43‐IR was apparent 4 days after ADX, and this increase was sustained at 7 and 14 days post‐ADX. The percentage of corticotrophs in apparent contact with GAP‐43‐IR axons was 87% at 4 days after ADX and 92% at 14 days. In addition, fewer than 15% of GAP‐43‐IR terminals were associated with cells other than corticotrophs in either group. This highly specific targeting of corticotrophs during a period in which these cells are undergoing both hypertrophy and hyperplasia indicates that axonal sprouting is occurring in response to ADX. While the less intense GAP‐43‐IR in the AP of intact rats precluded precise quantitative analysis, the majority of corticotrophs also appeared to be selectively innervated in these animals. The observations that GAP‐43‐IR axons selectively contact corticotrophs, and that both the specificity and thoroughness of innervation are maintained by targeted growth of GAP‐43‐IR axons following ADX, strongly suggest that these fibers are of functional significance.