Galanin, a brain-gut peptide, is also synthesized and released by the pituitary. In man, galanin-like immunoreactivity and galanin messenger RNA have been detected specifically in normal and tumoral corticotropes, but little is known about the production and release of galanin by the human pituitary. We evaluated galanin release by 5 ACTH-secreting pituitary adenomas in culture and plasma galanin concentrations in the inferior petrosal sinuses (IPSs) of 15 patients with Cushing's disease before and after CRH administration. For comparison, the galanin response to CRH was evaluated in 8 normal controls. Galanin secretion by pituitary tumor cultures ranged from 30-230 pmol/4 h. Incubation with CRH induced an increase in galanin concentrations (100 pM CRH: 151 +/- 32%; 1 nM CRH: 232 +/- 43%; 10 nM CRH: 246 +/- 35%; and 100 nM CRH: 270 +/- 44% unstimulated levels at 24 h, P < 0.05). The stimulatory effect of CRH seemed to be dose-dependent. Basal and CRH-stimulated ACTH and galanin concentrations also exhibited a strong positive correlation in single tumor cultures. At IPS sampling, mean basal plasma galanin concentrations in the dominant IPS were somewhat higher than those registered at the periphery (18.6 +/- 1.94 vs. 15.8 +/- 1.60 pmol/L, P = 0.05). Administration of CRH induced a modest but significant increase in galanin concentrations at all three sampling sites. No correlations were found between ACTH and galanin levels in the IPSs and at the periphery. Different from what was observed in patients with Cushing's disease, CRH did not modify plasma galanin concentrations in normal subjects. In conclusion, this study demonstrates that galanin is released by human tumoral corticotropes and responds to CRH. The role of locally produced galanin is, as yet, unknown but may possibly be that of a autocrine/paracrine modulator.