title: Interaction between glucagon and hexarelin, a peptidyl GH secretagogue, on somatotroph and corticotroph secretion in humans.
abstract: OBJECTIVE
  Glucagon administration stimulates both somatotroph and corticotroph secretion in humans, although this happens only if glucagon is administered by the intramuscular route and not by the intravenous route. On the other hand, GH secretagogues (GHS) strongly stimulate GH and also possess ACTH-releasing activity.
  
  
  METHODS
  To clarify the mechanisms underlying the stimulatory effects of both glucagon and GHS on somatotroph and corticotroph secretion, we studied the GH, ACTH and cortisol responses to glucagon (GLU, 0.017 mg/kg i.m.) and Hexarelin, a peptidyl GHS (HEX, 2.0 microg/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).
  
  
  RESULTS
  GLU administration elicited a clear increase in GH (peak vs baseline, mean+/-S.E.M.: 11.6+/-3.4 vs 3. 3+/-0.7 microg/l, P<0.02), ACTH (11.6+/-3.3 vs 4.1+/-0.3 pmol/l, P<0. 02) and cortisol (613.5+/-65.6 vs 436.9+/-19.3 nmol/l, P<0.05) levels. HEX induced a marked increase in GH levels (55.7+/-19.8 vs 3. 7+/-1.9 microg/l, P<0.005) and also significant 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 the curve (AUC) after HEX was clearly higher than after GLU (1637.3+/-494.0 vs 479.1+/-115. 7 microg/l/120 min, P<0.04) while HEX and GLU coadministration had a true synergistic effect on GH release (3243.8+/-687.5 microg/l/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 min and 18 874.5+/-1626.1 vs 28 338.5+/-2430.7 nmol/l/120 min 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 (35 424.6+/-5548.1 nmol/l/120 min) secretion.
  
  
  CONCLUSIONS
  These results show that the intramuscular administration of glucagon releases less GH but more ACTH and cortisol than Hexarelin. The combined administration of glucagon and Hexarelin has a true synergistic effect on somatotroph secretion but a less than additive effect on corticotroph secretion; these findings suggest that these stimuli act via different mechanisms to stimulate somatotrophs while they could have a common action on the hypothalamo-pituitary-adrenal axis.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Arvat
authors.forename: B
authors.initials: B
authors.lastname: Maccagno
authors.forename: J
authors.initials: J
authors.lastname: Ramunni
authors.forename: R
authors.initials: R
authors.lastname: Giordano
authors.forename: F
authors.initials: F
authors.lastname: Broglio
authors.forename: L
authors.initials: L
authors.lastname: Gianotti
authors.forename: M
authors.initials: M
authors.lastname: Maccario
authors.forename: F
authors.initials: F
authors.lastname: Camanni
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000494:pharmacology*; D005934:Glucagon / Q000009:adverse effects / Q000494:pharmacology*; D006133:Growth Substances / Q000009:adverse effects / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007273:Injections, Intramuscular; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology*; D011863:Radioimmunoassay
chemical_list: D005765:Gastrointestinal Agents; D006133:Growth Substances; D009842:Oligopeptides; C086184:hexarelin; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D006854:Hydrocortisone