CHARACTERIZATION OF THE PARADOXICAL GROWTH-HORMONE INHIBITORY EFFECT OF GALANIN IN ACROMEGALY

Galanin is a 29-amino acid straight-chain biologically active peptide which has been found to decrease circulating GH levels in some acromeg alic patients, whereas is able to increase GH secretion in normal subj ects. The aim of our study was to ascertain the incidence, entity and mechanism of the paradoxical GH inhibitory effect of galanin in acrome galy also looking at possible correlations between the GH responses to galanin and the main clinical and biochemical features of the patient s. Finally, the effects of either successful or unsuccessful neurosurg ical intervention on the GH inhibitory effect of galanin in acromegaly were investigated. A series of 23 consecutive patients with active ac romegaly seen at the Endocrine Section of the Department of Internal M edicine of the University of Brescia (Italy) between 1991 and 1994 was examined. The acromegalic patients were subdivided in group I (i.e. p atients who were 1) untreated, 2) evaluated before surgery, and 3) not cured after surgery and radiotherapy) and group 2 (i.e. surgically cu red). All patients were submitted at least once to the following bioch emical and radiological evaluations: 1) baseline serum insulin-like gr owth factor-I and PRL samples, 2) iv infusion of synthetic porcine gal anin (500 mu g in 100 mL saline) from -10 to 30 min, 3) iv bolus injec tion of TRH (200 mu g) at time zero, 4) oral glucose tolerance test (7 5 g glucose, orally) at time zero, and 5) magnetic resonance of the pi tuitary sella. Adenomatous tissue obtained during neurosurgery in four patients was cultured in vitro, and the effect of the addition of gal anin in the culture medium on GH secretion was tested. During galanin infusion in 19 of 21 group 1 patients, serum GH levels were lower with respect to baseline (range of GH decrease, -6.2 to -85.4% with respec t to basal levels). During galanin infusion, no reductions in GH level s were observed in the acromegalic patients cured after neurosurgery ( group 2); on the contrary, 6 of 7 patients displayed a normal stimulat ory response to galanin (range of GH increase, + 120-1533.3% of the ba sal level). A significant correlation between the percent decrease in GH levels after galanin treatment and the percent increase after TRH w as found in group 1 patients (r = -0.783; P < 0.05). In three of the f our adenomas examined, galanin determined a clear decrease in GH secre tion (mean nadir, 63.3 +/- 12% of the baseline secretion rate). In con clusion, we demonstrated that the large majority of numerous patients with active acromegaly show a decrease in serum GH levels after galani n administration. This effect, variable in magnitude, is exerted direc tly at the pituitary level, probably through an interaction with speci fic receptors expressed by the adenomatous cells.