Influence of galanin and serotonin on the endocrine response to Hexarelin, a synthetic peptidyl GH-secretagogue, in normal women.

Hexarelin (HEX) is a synthetic GH-secretagogue (GHS) which acts on specific receptors either at the pituitary or the hypothalamic level to stimulate GH release both in animal and in man. Like other GHS, HEX possesses also PRL-, ACTH- and cortisol (F)-releasing activity but the mechanisms underlying these effects are even less clear. On the other hand, galanin (GAL) and serotonin play an important role in the neural control of GH, PRL and ACTH secretion both in animal and in man. In order to study the interaction between HEX and GAL and to verify whether serotoninergic mechanisms underly the endocrine effects of GHS, in 12 normal young volunteers (24-30 yr) the following tests were performed: group A (N = 5), HEX (2.0 micrograms/kg i.v. at 0 min), GAL (15.0 micrograms/kg i.v. from 0 to 60 min) and HEX + GAL; group B (N = 7), HEX alone and preceeded by cyproeptadine (CYPRO, 8 mg os at -60 min). In group A, the GH response to HEX (1204.2 +/- 312.9 microgramsmin/L) was higher (p < 0.05) than that to GAL alone (305.6 +/- 35.5 microgramsmin/L) and was not modified by GAL co-administration (1021.8 +/- 249.9 microgramsmin/L). PRL secretion was increased to the same extent by HEX and GAL (507.9 +/- 81.1 and 743.0 +/- 164.7 microgramsmin/L) which showed no interaction (603.5 +/- 75.7 microgramsmin/L). HEX elicited an increase in both ACTH and F secretion (924.5 +/- 169.7 pgmin/ml and 6131.3 +/- 616.6 microgramsmin/L) while GAL had no effect when given alone (759.5 +/- 185.5 pgmin/ml and 5350.3 +/- 755.6 microgramsmin/L) and did not modify the effect of HEX (891.3 +/- 159.2 pgmin/ml and 5877.8 +/- 554.4 microgramsmin/L). In group B, the GH response to HEX (1636.4 +/- 267.5 microgramsmin/L) was blunted by CYPRO (1164.8 +/- 212.3 microgramsmin/L) but this difference did not attained statistical significance. On the other hand, CYPRO did not modify the HEX-induced PRL (599.5 +/- 129.2 vs 638.9 +/- 131.9 microgramsmin/L), ACTH (1282.8 +/- 222.0 vs 1330.2 +/- 347.0 pgmin/ml) and F response (4738.3 +/- 355.3 vs 4580.9 +/- 857.3 microgramsmin/L). Our present data demonstrate that Hexarelin has no interaction with galanin; thus thereotically, the stimulatory effect of GHS on GH and PRL secretion could involve, at least partially, a galanin-mediated mechanism. On the other hand, our data demonstrate that serotonin does not mediate the stimulatory effect of GHS on PRL, ACTH and cortisol; the intrinsic anticholinergic property of cyproeptadine could account for the trend toward its blunting effect on the GH response to Hexarelin.