TY - JOUR
T1 - Putative somatostatin suppression potentiates adrenocorticotropin secretion driven by ghrelin and human corticotropin-releasing hormone
AU - Iranmanesh, Ali
AU - Carpenter, Paul C.
AU - Mielke, Kristi
AU - Bowers, Cyril Y.
AU - Veldhuis, Johannes D.
N1 - Funding Information:
This work was supported in part via General Clinical Research Center Grant MO1 RR00585 to the Mayo Clinic and Foundation from the National Center for Research Resources (Rockville, MD) and R01 NIA AG 19695 and DK 073148 from the National Institutes of Health (Bethesda, MD).
PY - 2007/9
Y1 - 2007/9
N2 - Context: Ghrelin is a 28-amino-acid Ser3-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.
AB - Context: Ghrelin is a 28-amino-acid Ser3-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.
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U2 - 10.1210/jc.2007-0523
DO - 10.1210/jc.2007-0523
M3 - Article
C2 - 17566099
AN - SCOPUS:34548771936
SN - 0021-972X
VL - 92
SP - 3653
EP - 3659
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -