Document Detail

Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity.
MedLine Citation:
PMID:  8473389     Owner:  NLM     Status:  MEDLINE    
GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP-6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state.
F Cordido; A Peñalva; C Dieguez; F F Casanueva
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  76     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1993 Apr 
Date Detail:
Created Date:  1993-05-18     Completed Date:  1993-05-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  819-23     Citation Subset:  AIM; IM    
Endocrine Section Hospital General de Galicia, Santiago de Compostela, Spain.
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MeSH Terms
Drug Combinations
Growth Hormone / blood,  secretion*
Growth Hormone-Releasing Hormone / pharmacology*
Injections, Intravenous
Middle Aged
Obesity / metabolism*,  pathology
Oligopeptides / pharmacology*
Pituitary Gland, Anterior / pathology,  secretion*
Pyridostigmine Bromide / pharmacology
Reg. No./Substance:
0/Drug Combinations; 0/Oligopeptides; 101-26-8/Pyridostigmine Bromide; 87616-84-0/growth hormone releasing hexapeptide; 9002-72-6/Growth Hormone; 9034-39-3/Growth Hormone-Releasing Hormone
Comment In:
J Clin Endocrinol Metab. 1993 Apr;76(4):817-8   [PMID:  8473388 ]

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