Growth hormone response to growth hormone-releasing hormone (GHRH), insulin, clonidine and arginine after GHRH pretreatment in obese children: evidence of somatostatin increase?

Abstract

To clarify the possible neuroendocrine mechanisms underlying the impairment in growth hormone (GH) secretion present in obesity, the GH response to GH-releasing hormone (GHRH, N = 6), insulin hypoglycemia (N = 6), clonidine (N = 7) and arginine (N = 8) after GHRH pretreatment (1 microgram/kg iv 2 h before the tests) was evaluated in 27 obese peripubertal children and in a group of normal-weight short-normal children (N = 26). Growth hormone-releasing hormone pretreatment and all further stimuli elicited a statistically significant GH response in both obese and short-normal children; in the latter group arginine did not induce a significant GH response. No differences were found among the GH responses after the second stimuli in obese children, while in short-normal children the arginine peak and area values were lower than after GHRH and clonidine. Comparison between the two groups showed similar baseline but higher stimulated GH levels in normal-weight children after all tests except arginine, after which no difference was present. In conclusion, the neuroregulation of GH release seems to be similar qualitatively in normal-weight and obese youngsters; the different behavior observed after arginine, which is supposed to act through somatostatin inhibition, might be due to a chronic increase in somatostatinergic tone responsible for the lower stimulated GH levels in obesity.

Growth Failure in Prader-Willi Syndrome Is Secondary to Growth Hormone Deficiency

“…It is also theorized that obesity is associated with increased somatostatin tone. Studies have found that arginine and pyridostigmine, both somatostatin inhibitors, significantly enhance GH release in obese children who had been treated with GH-releasing hormone [6, 13]. It should be noted, however, that pyridostigmine has been found to enhance GH secretion after GHRH treatment in children with GH deficiency, familial short stature, and constitutional growth delay, as well [14].…”

GH/IGF-I Regulation in Obesity – Mechanisms and Practical Consequences in Children and Adults

“…Indirect studies in humans using somatostatin infusion seem to support this notion as the relative GH/IGF-I response during somatostatin infusion and following withdrawal was comparable [12]. In obese and normal-weight children in whom the GH response to various stimuli was assessed after growth hormone-releasing hormone (GHRH) pretreatment, obese children exhibited similarly high GH levels as the normal weight control group only after stimulation with arginine, which is believed to act via somatostatin inhibition [13]. The alternative explanation of a GHRH hypofunction in obesity has not, however, been experimentally substantiated.…”

Effects of arginine, growth hormone-releasing hormone (GHRH) and neostigmine administered singly or in paired combinations on growth hormone (GH) release in pigs

“…ARG-induced GH release has been welldocumented in human and is thought to be mediated by a decrease in somatostatin release (Locatelli et al, 1986;Alba-Roth et al, 1988;Ghigo et al, 1990a;Volta et al, 1995). In that respect, ARG has been shown to override inhibitory effects on GH secretion that are known to be mediated by an increase in somatostatin release, including glucose administration (Ghigo et al, 1992), obesity Martina et al, 1995), glucocorticoids (Giustina et al, 1992), advanced age (Ghigo et al, 1990b) and GH negative feedback (Massara et al, 1986;Torsello et al, 1988;Kelijman and Frohman, 1991;Ghigo et al, 1991).…”