Putative somatostatin suppression potentiates adrenocorticotropin secretion driven by ghrelin and human corticotropin-releasing hormone.

Author(s): Iranmanesh A, Carpenter PC, Mielke K, Bowers CY, Veldhuis JD

Affiliation(s): Endocrine Section, Department of Medicine, Salem Veterans Affairs Medical Center, Salem, Virginia 24153, USA.

Publication date & source: 2007-09, J Clin Endocrinol Metab., 92(9):3653-9. Epub 2007 Jun 12.

Publication type: Research Support, N.I.H., Extramural

CONTEXT: 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. DESIGN AND SETTING: We conducted a randomized, double-blind, placebo-controlled, crossover interventional study at an academic medical center. PARTICIPANTS: Ten healthy postmenopausal women participated in the study. INTERVENTIONS: 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). OUTCOME MEASURES: 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.