TY - JOUR
T1 - Ghrelin potentiates growth hormone secretion driven by putative somatostatin withdrawal and resists inhibition by human corticotropin-releasing hormone
AU - Veldhuis, Johannes D.
AU - Iranmanesh, Ali
AU - Mielke, Kristi
AU - Miles, John M.
AU - Carpenter, Paul C.
AU - Bowers, Cyril Y.
PY - 2006
Y1 - 2006
N2 - Context: Ghrelin is a 28-amino acid, Ser3-octanoylated peptide that stimulates GH secretion in vivo and in vitro. Beyond the capability of ghrelin to synergize with GHRH, little is known about multipeptide modulation of ghrelin's actions in humans. Objective: The objective of this study was to test the hypothesis that ghrelin can stimulate GH secretion in the absence or presence of somatostatin withdrawal (induced by L-arginine infusion) and stress-like drive by CRH. Design: This was a randomized, double-blind, placebo-controlled, cross-over interventional study. Setting: This study was performed at an academic medical center. Participants: Nine healthy postmenopausal women not receiving sex hormones were studied. Interventions: Subjects were given an iv infusion of saline and/or L-arginine or human CRH, followed by a bolus iv injection of ghrelin. Outcome Measures: The outcome measures were pulsatile GH secretion quantified by repetitive blood sampling, immunochemiluminometry, and deconvolution analysis. Results: Consecutive saline/ghrelin infusion increased pulsatile GH secretion from 2.7 ± 1.0 (saline/saline; mean ± SEM) to 20 ± 5.0 μg/liter·3 h (P < 0.01). The magnitude of the effect of L-arginine/saline was comparable at 20 ± 4.5 μg/liter·3 h (P < 0.01). In contrast, sequential L-arginine/ghrelin evoked true synergy of GH release (93 ± 14 μg/liter·3h; P = 0.003 vs. L-arginine alone and P = 0.008 vs. ghrelin alone). Human CRH did not affect GH responses to saline/saline (3.9 ± 1.1 μg/liter·3 h), saline/ghrelin (19 ± 3.3 μg/liter·3 h), L-arginine/saline (16 ± 2.7 μg/liter·3 h), or L-arginine/ghrelin (90 ± 13 μg/liter·3 h). Conclusions: Assuming that L-arginine reduces somatostatin outflow, we infer that ghrelin can activate hypothalamo-pituitary pathways that are both dependent upon and independent of somatostatinergic restraint even in the face of a strong stress-related signal.
AB - Context: Ghrelin is a 28-amino acid, Ser3-octanoylated peptide that stimulates GH secretion in vivo and in vitro. Beyond the capability of ghrelin to synergize with GHRH, little is known about multipeptide modulation of ghrelin's actions in humans. Objective: The objective of this study was to test the hypothesis that ghrelin can stimulate GH secretion in the absence or presence of somatostatin withdrawal (induced by L-arginine infusion) and stress-like drive by CRH. Design: This was a randomized, double-blind, placebo-controlled, cross-over interventional study. Setting: This study was performed at an academic medical center. Participants: Nine healthy postmenopausal women not receiving sex hormones were studied. Interventions: Subjects were given an iv infusion of saline and/or L-arginine or human CRH, followed by a bolus iv injection of ghrelin. Outcome Measures: The outcome measures were pulsatile GH secretion quantified by repetitive blood sampling, immunochemiluminometry, and deconvolution analysis. Results: Consecutive saline/ghrelin infusion increased pulsatile GH secretion from 2.7 ± 1.0 (saline/saline; mean ± SEM) to 20 ± 5.0 μg/liter·3 h (P < 0.01). The magnitude of the effect of L-arginine/saline was comparable at 20 ± 4.5 μg/liter·3 h (P < 0.01). In contrast, sequential L-arginine/ghrelin evoked true synergy of GH release (93 ± 14 μg/liter·3h; P = 0.003 vs. L-arginine alone and P = 0.008 vs. ghrelin alone). Human CRH did not affect GH responses to saline/saline (3.9 ± 1.1 μg/liter·3 h), saline/ghrelin (19 ± 3.3 μg/liter·3 h), L-arginine/saline (16 ± 2.7 μg/liter·3 h), or L-arginine/ghrelin (90 ± 13 μg/liter·3 h). Conclusions: Assuming that L-arginine reduces somatostatin outflow, we infer that ghrelin can activate hypothalamo-pituitary pathways that are both dependent upon and independent of somatostatinergic restraint even in the face of a strong stress-related signal.
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U2 - 10.1210/jc.2005-2718
DO - 10.1210/jc.2005-2718
M3 - Article
C2 - 16537682
AN - SCOPUS:33744953964
SN - 0021-972X
VL - 91
SP - 2441
EP - 2446
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -