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Aim of our study was to investigate the effect of clonidine and galanin (alone or in combination) on growth hormone (GH) secretion in normal subjects and in adult patients with increased somatostatin tone due to chronic daily immunosuppressive glucocorticoid treatment. We studied 7 adult patients undergoing long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for non endocrine diseases (4F, 3M; age 49.7 +/- 6.3 years). Six normal adult nonobese subjects (3F, 3M; age 34 +/- 2.7 years) served as controls. All subjects underwent the following three tests in random order: 1) iv infusion of clonidine, 150 micrograms in 10 mL of saline, from time 0 to 10 min; 2) iv infusion of synthetic porcine galanin, 500 micrograms in 100 mL of saline from -15 to 30 min; 3) iv infusion of clonidine from 0 to 10 min combined with synthetic porcine galanin iv infusion from -15 to 30 min. Blood samples for GH assay were taken at -15, 0, 15, 30, 45, 60, 90, 120 min. No significant differences in GH absolute values were observed at any time between the three different tests within each group of subjects. Normal subjects showed significantly (p < 0.05) higher GH peaks and GH absolute values from 15 to 90 min after galanin alone, clonidine alone and clonidine+galanin with respect to the glucocorticoid-treated patients. The absence of any either synergistic or at least additive effect on GH secretion of galanin and clonidine in conditions of both normal and increased somatostatin tone suggests that also in man, as well as in the rat, the action of galanin on the GH axis may be mediated through alpha-adrenergic pathways.

Galanin is able to enhance growth hormone (GH)-releasing hormone stimulated GH secretion in normal man. In acromegaly circulating GH levels are elevated and the GH response to GHRH may be exaggerated. Galanin has been recently shown to decrease circulating GH levels in acromegaly. Dopaminergic drugs were the only previously known agents able to cause a paradoxical GH fall in acromegaly. Aim of our study was to investigate the effects of a potent central dopaminergic receptor blocker, metoclopramide (MCP), on the galanin-induced paradoxical GH secretion in acromegalic subjects. Two male and three female patients with active acromegaly (age range 44-66 years, body mass index range 24.6-28 Kg/m2) were studied after 45 min i.v. infusion of porcine galanin (0.5 mg in 100 ml of saline) from 0 to 45 min combined with a 60 min i.v. infusion of a) saline (100 ml) or b) MCP (10 mg in 100 ml of saline) from -15 to 45 min. After galanin, GH values fell from baseline (27.5 +/- 10 micrograms/L) to a mean nadir of 16.4 +/- 6.1 micrograms/L; after galanin + MCP, circulating GH levels were also decreased (mean nadir 17.3 +/- 8.1 micrograms/L) in all the patients with respect to baseline (23.6 +/- 9.7 micrograms/L). No significant differences were found in absolute or percent of baseline GH levels after galanin+saline vs galanin + MCP. Our results suggest that the paradoxical GH fall after galanin in acromegalic patients is not mediated through dopaminergic receptor. It can be hypothesized that galanin may interact at the pituitary level with its own receptors expressed by GH-secreting adenomatous cells.

Attenuated plasma GH secretion during sleep and blunted GH responses to provocative stimuli have been observed in patients with Cushing's disease. Synthetic porcine galanin elicits GH secretion when given alone, and enhances the GH response to GHRH in normal human subjects. The aim of our study was to investigate the effects of galanin on the GH response to GHRH in patients with Cushing's disease. We studied 5 female subjects with untreated active Cushing's disease caused by micro-pituitary adenomas (age 43 +/- 6.7 years; BMI 30 +/- 0.7 kg/m2). Four normal adult females, matched for age and body weight with the patients with Cushing's disease, were studied as controls. Subjects underwent in random order: (1) infusion of synthetic porcine galanin IV, 500 micrograms in 100 mL; (2) infusion of saline, IV, 100 mL. A bolus of human GHRH(1-29)NH2 (Geref, Serono, Italy), 100 micrograms in 1 mL saline, was injected IV at 0 minutes. Patients with Cushing's disease showed blunted GH peaks after GHRH (1.2 +/- 0.4 micrograms/L) during saline infusion, as compared to normal controls (24.6 +/- 4.6 micrograms/L; p < 0.05). During galanin infusion a significantly enhanced GH response to GHRH, as compared with saline infusion, was observed in control subjects (GH peak: 51.4 +/- 9.8 micrograms/L; p < 0.05), but not in patients with Cushing's disease (GH peak: 2.3 +/- 0.6 micrograms/L). GH levels were significantly lower both after saline and after galanin in patients with Cushing's disease as compared to normal controls. Our data demonstrate that galanin is not able to enhance the GH response to GHRH in patients with Cushing's disease. That galanin cannot reverse this effect suggests that the mechanism of action of galanin is not via a decrease in somatostatin release by the hypothalamus.