title: 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.
abstract: 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.
authors: Endocrine Section Hospital General de Galicia, Santiago de Compostela, Spain.
authors: F
authors: F
authors: Cordido
authors: A
authors: A
authors: Peñalva
authors: C
authors: C
authors: Dieguez
authors: F F
authors: FF
authors: Casanueva
mesh_terms: D000293:Adolescent; D000328:Adult; D004338:Drug Combinations; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000473:pathology; D011729:Pyridostigmine Bromide / Q000494:pharmacology
chemical_list: D004338:Drug Combinations; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D011729:Pyridostigmine Bromide