Effect of combined administration of growth hormone (GH)-releasing hormone, GH-releasing peptide-6, and pyridostigmine in normal and obese subjects

Abstract

Growth hormone (GH) secretion in response to all provocative stimuli is decreased in patients with obesity. Recently, we found that the combined administration of GH-releasing hormone (GHRH) and the hexapeptide GH-releasing peptide-6 (GHRP-6) induced a large increase in plasma GH levels. To gain further insight into the disrupted mechanism of GH regulation in obesity, we investigated whether the inhibition of somatostatinergic tone with pyridostigmine could further increase the GH response to combined administration of GHRH and GHRP-6. In normal subjects, administration of GHRH plus GHRP-6 induced a marked increase in plasma GH with a peak at 30 minutes (mean ± SEM, 76.7 ± 9.7 μg/L), which was similar to that obtained after pretreatment with pyridostigmine (74.7 ± 9.4 μg/ L). In obese patients, combined administration of GHRH plus GHRP-6 induced a clear increase in GH secretion with a peak at 15 minutes of 42.2 ± 10.0 μg/L, which was also unaffected after pretreatment with pyridostigmine (38.4 ± 5.8 μg/L). The GH response was lower in obese patients than in controls as assessed by the area under the curve after administration of both GHRH plus GHRP-6 (1,846 ± 396 v 4,773 ± 653, P < .01) and pyridostigmine plus GHRH plus GHRP-6 (1,989 ± 372 v 5,098 ± 679, P < .005). In conclusion, these data suggest that GHRP-6 can behave as a functional somatostatin antagonist, and that somatotrope responsiveness to the combined administration of GHRH plus GHRP-6 is largely independent of somatostatinergic tone. Therefore, our findings in obese subjects of a relatively high GH response to GHRH plus GHRP-6, albeit low in comparison to that in normal subjects, with or without pyridostigmine suggest that the somatotrope cell in obesity has a considerable GH secretory capacity.