1. Growth hormone releasing hexapeptide-6 (GHRP-6) test in the diagnosis of GH-deficiency
M Pombo, A Leal-Cerro, J Barreiro, A Peñalva, R Peino, F Mallo, C Dieguez, F F Casanueva J Pediatr Endocrinol Metab. 1996 Jun;9 Suppl 3:333-8.
Pituitary GH reserve can be assessed by substances that act directly at the somatotroph, such as GHRH, or by a variety of metabolic and neuropharmacological tests acting at the hypothalamic level, such as hypoglycemia, clonidine or L-Dopa. In order to evaluate GHRP-6 as a test of pituitary GH reserve, we studied GH responses of i.v. administered GHRP-6 in a group of short-statured children, as well as in a group of adults diagnosed with growth hormone deficiency (GHD) by conventional GH testing. Although we found that the GH response to GHRP-6 was lower in patients with GHD than in normal children, on an individual basis a considerable degree of overlap was observed between the two groups. In contrast, we found an almost complete blockade of GH response to either GHRP-6 or GHRH plus GHRP-6 in patients with pituitary stalk transection, suggesting that this could be a cost-effective test for the diagnosis of this condition. A similar finding was also obtained in GH response to the combined administration of GHRH plus GHRP-6 in patients with GHD of adult onset; this test may well prove valuable in the diagnosis of this clinical entity.
2. Regulation of growth hormone secretion by the growth hormone releasing hexapeptide (GHRP-6)
D Micic, F Mallo, R Peino, F Cordido, A Leal-Cerro, R V Garcia-Mayor, F F Casanueva J Pediatr Endocrinol. 1993 Jul-Dec;6(3-4):283-9. doi: 10.1515/jpem.1993.6.3-4.283.
Growth hormone (GH) secretion is regulated by a complex system of central and peripheral signals. Recently, a new GH-releasing hexapeptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) called GHRP-6 which specifically releases GH has been studied. In the present work the mechanism of action of GHRP-6 has been addressed in experimental animal models as well as in obese subjects. GHRP-6 releases GH independently of the hypothalamic factors GHRH and somatostatin and is a powerful GH releaser in obesity.
3. [D-Lys3]-GHRP-6 exhibits pro-autophagic effects on skeletal muscle
Angus P Yu, Xiao M Pei, Thomas K Sin, Shea P Yip, Benjamin Y Yung, Lawrence W Chan, Cesar S Wong, Parco M Siu Mol Cell Endocrinol. 2015 Feb 5;401:155-64. doi: 10.1016/j.mce.2014.09.031. Epub 2014 Oct 29.
[D-Lys3]-GHRP-6 is regarded as a highly selective growth-hormone secretagogue receptor (GHSR) antagonist and has been widely used to investigate the dependency of GHSR-1a signalling mediated by acylated ghrelin. However, [D-Lys3]-GHRP-6 has been reported to influence other cellular processes which are unrelated to GHSR-1a. This study aimed to examine the effects of [D-Lys3]-GHRP-6 on autophagic and apoptotic cellular signalling in skeletal muscle. [D-Lys3]-GHRP-6 enhanced the autophagic signalling demonstrated by the increases in protein abundances of beclin-1 and LC3 II-to-LC3 1 ratio in both normal muscle and doxorubicin-injured muscle. [D-Lys3]-GHRP-6 reduced the activation of muscle apoptosis induced by doxorubicin. No histological abnormalities were observed in the [D-Lys3]-GHRP-6-treated muscle. Intriguingly, the doxorubicin-induced increase in centronucleated muscle fibres was not observed in muscle treated with [D-Lys3]-GHRP-6, suggesting the myoprotective effects of [D-Lys3]-GHRP-6 against doxorubicin injury. The [D-Lys3]-GHRP-6-induced activation of autophagy was found to be abolished by the co-treatment of CXCR4 antagonist, suggesting that the pro-autophagic effects of [D-Lys3]-GHRP-6 might be mediated through CXCR4. In conclusion, [D-Lys3]-GHRP-6 exhibits pro-autophagic effects on skeletal muscle under both normal and doxorubicin-injured conditions.
