Hyperinnervation during adrenal regeneration influences the rate of functional recovery

The rat adrenal cortex has the uncommon ability to demonstrate morphologica l and functional regeneration after injury-induced loss of cortical tissue. Peripheral nerves are involved in tissue regeneration and healing after in jury, implying that nerves may also be involved in modulating the regenerat ion of the adrenal cortex. Studies were initiated to assess changes in adre nal innervation during cortical tissue regeneration subsequent to adrenal e nucleation. Innervation of regenerating adrenals was assessed from 3 to 62 days postenucleation by immunohistofluorescent detection of neuronal marker s for primary afferent, preganglionic sympathetic, and postganglionic sympa thetic fibers. The regenerating adrenal contained few nerves at 3 days post enucleation, but became differentially innervated, with extensive innervati on by nerve fibers positive for calcitonin gene-related peptide (CGRP), tyr osine hydroxylase (TH), neuropeptide Y (NPY), and neuronal nitric oxide syn thase (nNOS). In contrast, there was only minimal innervation by nerve fibe rs positive for vasoactive intestinal peptide. By 14 days postenucleation, the CGRP-, TH-, and NPY-positive innervation included areas of hyperinnerva tion in the capsule, cortex, and central inflammatory site of the regenerat ing gland. In addition, many chromaffin cells were present at all time poin ts postenucleation. Quantification of the regenerating gland content of CGR P, norepinephrine, epinephrine, and nNOS verified the immunohistofluorescen t observations. The period of extensive innervation correlated temporally w ith the time (3-30 days) during which the regenerating glands recovered ste roidogenic function. Moreover, splanchnic nerve transection at the time of adrenal enucleation decreased the innervation by CGRP-positive and vesicula r acetylcholine transporter-positive fibers and delayed regeneration. These results support the hypothesis that adrenal innervation modulates tissue r egeneration and functional recovery of the enucleated adrenal gland. Copyri ght (C) 2000 S. Karger AG, Basel.