Interaction between glucagon and Hexarelin, a peptidyl GH secretagogue, onsomatotroph and corticotroph secretion in humans

Objective: Glucagon administration stimulates both somatotroph and corticot roph secretion in humans, although this happens only if glucagon is adminis tered by the intramuscular route and not by the intravenous route. On the o ther hand, GH secretagogues (GHS) strongly stimulate GH and also possess AC TH-releasing activity. Design and Methods: To clarify the mechanisms underl ying the stimulatory effects of both glucagon and GHS on somatotroph and co rticotroph secretion, we studied the GH, ACTH and cortisol responses to glu cagon (GLU, 0.017 mg/kg i.m.) and Hexarelin, a peptidyl GHS (HM, 2.0 mug/kg i.v.) given alone or in combination In 6 normal young volunteers (females, aged 26-32 years, body mass index 19.7-22.5 kg/m(2)). Results: GLU administration elicited a clear increase in GH (peak vs baseli ne, mean+/-S.E.M.: 11.6 +/- 3.4 vs 3.3 +/- 0.7 mug/l, P < 0.02), ACTH (11.6 +/- 3.3 vs 4.1 +/- 0.3 pmol/l, P < 0.02) acid cortisol (613.5 +/- 65.6 vs 436.9 +/- 13.3 nmol/l, P < 0.05) levels. HEX induced a marked increase in G H levels (55.7 +/- 19.8 vs 3.7 +/- 1.9 <mu>g/l P < 0.005) and also signific ant ACTH (5.7 +/- 1.1 vs 3.4 +/- 0.6 pmol/l, P < 0.01) and cortisol (400.2 +/- 31.4 vs 363.4 +/- 32.2 nmol/l, P < 0.05) responses. The GH area under t he curve (AUC) after HEX was clearly higher than after GLU (1637.3 +/- 494. 0 vs 479.1 +/- 115.7 <mu>g/1/120 min, P < 0.04) while HEX and GLU coadminis tration had a true synergistic effect on GH release (3243.8 +/- 687.5 <mu>g /1/120 min, P < 0.02). The ACTH and cortisol AUCs after HEX were lower (P < 0.02) than those after GLU (208.3 +/- 41.3 vs 426.3 +/- 80.9 pmol/l/120 mi n and 18 874.5 +/- 1626.1 vs 28 338.5 +/- 2430.7 nmol/1/120min respectively ). The combined administration of HEX and GLU had an effect which was less than additive on both ACTH (564.02 +/- 76.5 pmol/l/120 min) and cortisol (3 5424.6 +/- 5548.1 nmol/l/120 min) secretion. Conclusions: These results show that the intramuscular administration of gl ucagon releases less GH but more ACTH and cortisol than Hexarelin. The comb ined administration of glucagon and Hexarelin has a true synergistic effect on somatotroph secretion but a less than additive effect on corticotroph s ecretion; these findings suggest that these stimuli act via different mecha nisms to stimulate somatotrophs while they could have a common action on th e hypothalamo-pituitary adrenal axis.