The GH-releasing effect of ghrelin, a natural GH secretagogue, is only blunted by the infusion of exogenous somatostatin in humans.
OBJECTIVE
Ghrelin, a 28-amino-acid peptide purified from the stomach and showing a unique structure with an n-octanoyl ester at the serine 3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R). Ghrelin strongly stimulates GH secretion in both animals and humans, showing a synergistic effect with GH-releasing hormone (GHRH) but no interaction with synthetic GHS. However, the activity of ghrelin as well as that of non-natural GHS is not fully specific for GH; ghrelin also induces a stimulatory effect on lactotroph and corticotroph secretion, at least in humans.


METHODS
To further clarify the mechanisms underlying the GH-releasing activity of this natural GHS, we studied the effects of somatostatin (SS, 2.0 microg/kg/h from -30 to +90 min) on the endocrine responses to ghrelin (1.0 microg/kg i.v. at 0 min) in seven normal young male volunteers [age (mean +/- SEM) 28.6 +/- 2.9 years; body mass index (BMI) 22.1 +/- 0.8 kg/m2]. In the same subjects, the effect of SS on the GH response to GHRH (1.0 microm/kg i.v. at 0 min) was also studied.


METHODS
Blood samples were taken every 15 min from -30 up to +120 min. GH levels were assayed at each time point in all sessions; PRL, ACTH and cortisol levels were assayed after ghrelin administration alone and during SS infusion.


RESULTS
The GH response to ghrelin (hAUC0'-->120' 2695.0 +/- 492.6 microg min/l) was higher (P < 0.01) than that after GHRH (757.1 +/- 44.1 microg min/l). SS infusion almost abolished the GH response to GHRH (177.0 +/- 37.7 microg min/l, P < 0.01); the GH response to ghrelin was inhibited by SS (993.8 +/- 248.5 microg min/l, P < 0.01) but GH levels remained higher (P < 0.05) than with GHRH. Ghrelin induced significant increases in PRL, ACTH and cortisol levels and these responses were not modified by SS.


CONCLUSIONS
Ghrelin, a natural GHS-R ligand, exerts a strong stimulatory effect on GH secretion in humans and this effect is only blunted by an exogenous somatostatin dose which almost abolishes the GH response to GHRH. The stimulatory effect of ghrelin on lactotroph and corticotroph secretion is refractory to exogenous somatostatin, indicating that these effects occur through pathways independent of somatostatinergic influence.
Di Vito
Lidia
L
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Santiago de Compostela, Spain.
Broglio
Fabio
F
Benso
Andrea
A
Gottero
Cristina
C
Prodam
Flavia
F
Papotti
Mauro
M
Muccioli
Giampiero
G
Dieguez
Carlos
C
Casanueva
Felipe F
FF
Deghenghi
Romano
R
Ghigo
Ezio
E
Arvat
Emanuela
E
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D036361:Peptide Hormones; D010455:Peptides / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D013004:Somatostatin / Q000494:pharmacology*; D013268:Stimulation, Chemical
D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D006854:Hydrocortisone