Putative somatostatin suppression potentiates adrenocorticotropin secretion driven by ghrelin and human corticotropin-releasing hormone.
BACKGROUND
Ghrelin is a 28-amino-acid Ser(3)-octanoylated peptide, and CRH is a 41-amino-acid peptide, both of which stimulate ACTH secretion. In principle, actions of these agonists could be subject to inhibitory modulation by hypothalamic somatostatin (SS).


OBJECTIVE
Our objective was to test the hypothesis that endogenous SS restrains ghrelin and CRH-stimulated ACTH secretion, thereby linking all three, ghrelin, CRH, and SS, with ACTH secretion.


METHODS
We conducted a randomized, double-blind, placebo-controlled, crossover interventional study at an academic medical center.


METHODS
Ten healthy postmenopausal women participated in the study.


METHODS
Interventions included iv injection of saline, ghrelin, human CRH, or both after an infusion of saline vs. l-arginine to putatively inhibit SS outflow (eight visits per subject).


METHODS
ACTH concentrations quantified by repetitive blood sampling and immunochemiluminometry.


RESULTS
Infusion of ghrelin induced peak ACTH concentrations [median (range)] of 21 (17-28) compared with 16 (11-20) ng/liter after saline (P = 0.037). CRH and l-arginine infusion evoked ACTH peaks of 23 (14-48) and 31 (21-286) ng/liter, respectively (P = 0.037 and P = 0.005 vs. saline). l-Arginine enhanced stimulation by ghrelin by 1.43-fold (P = 0.028) and that by CRH by 1.91-fold (P = 0.005). Triple stimulation with ghrelin, CRH, and l-arginine potentiated the effect of combined ghrelin/CRH by 1.45-fold (P = 0.028). Downstream cortisol responses mimicked those of ACTH but were time delayed.


CONCLUSIONS
The present outcomes indicate that the peptide ensemble comprising ghrelin, CRH, and SS (inferred by l-arginine infusion) can regulate ACTH and cortisol secretion in healthy adults.
Iranmanesh
Ali
A
Endocrine Section, Department of Medicine, Salem Veterans Affairs Medical Center, Salem, Virginia 24153, USA.
Carpenter
Paul C
PC
Mielke
Kristi
K
Bowers
Cyril Y
CY
Veldhuis
Johannes D
JD
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000368:Aged; D001120:Arginine / Q000008:administration & dosage; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D054439:Ghrelin; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D036361:Peptide Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D010919:Placebos; D013004:Somatostatin / Q000037:antagonists & inhibitors*
D004338:Drug Combinations; D054439:Ghrelin; D036361:Peptide Hormones; D010919:Placebos; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D001120:Arginine