Galanin in human pituitary adenomas: frequency and clinical significance

Galanin (GAL) is a neuropeptide widely expressed in the central and peripheral nervous system and in neuroendocrine tissue, including the adenohypophysis where, in humans, it is expressed in corticotrophs and in ACTH-producing adenomas. Previous analyses of human tissue have used antiserum against porcine GAL for detection of GAL immunoreactivity (GAL-IR) and no pathophysiological correlates have been reported. Given significant differences between the sequence of porcine and human GAL peptides, the aim of this study was to use antiserum raised against synthetic human GAL to investigate GAL-IR in non tumorous pituitaries and in pituitary adenomas, and to correlate GAL-IR with the clinical and hormonal characteristics of patients with Cushing's disease.

Six nontumorous pituitaries were obtained from autopsy and 151 pituitary adenomas, comprising 62 functioning (16 corticotroph, 26 somatotroph, 19 lactotroph and one thyrotroph) and 89 nonfunctioning adenomas, were obtained by surgery.

All non tumorous pituitary glands showed GAL-IR in corticotrophs, in basophil cells within the neurohypophysis and in nerve fibres of the neurohypophysis. GAL-IR was found in a subset (10 of 16) of patients with ACTH-secreting tumours causing Cushing's syndrome. GAL-IR was rarely expressed in somatotroph adenomas and prolactinomas, but was expressed in approximately one-third of nonfunctioning tumours. GAL-IR was found in almost 90% of nonfunctioning tumours that were positive for ACTH. There were no significant differences in sex ratio, age at presentation or 24-h urinary free cortisol secretion in the subset of patients with Cushing's disease positive (n = 10) or negative (n = 6) for GAL-IR. However, Cushing's patients positive for GAL-IR tended to have smaller tumours and achieved a higher cure rate than those without (100 vs. 50%, P = 0.017).

Galanin is present in normal and tumorous human pituitaries. In addition, GAL colocalizes exclusively in corticotrophs of normal pituitaries and is coexpressed almost exclusively in corticotrophs from functioning and nonfunctioning tumours. The finding that corticotroph adenomas can function irrespective of the presence of GAL suggests that GAL may not play a pathophysiological role in Cushing's disease. However, the better surgical outcome observed in patients with Cushing's disease who had tumours positive for GAL-IR suggests that the expression of GAL confers a less aggressive tumour phenotype.