Influence of beta-adrenergic agonists and antagonists on the GH-releasing effect of Hexarelin in man

Abstract

Beta-adrenergic receptors mediate the inhibitory influence of cathecolamines on GH secretion, probably via the stimulation of hypothalamic somatostatin release. Accordingly, beta-adrenergic agonists and antagonists inhibit and increase, respectively, the GH response to many stimuli, including GHRH, in man. Aim of the present study was to verify the effect, if any, of beta-adrenergic drugs on the GH response to Hexarelin, a synthetic GH-releasing hexapeptide. Interestingly, the GH-releasing effect of Hexarelin has been reported to be partially refractory to neuroendocrine manipulations known to strongly enhance or abolish the GHRH-induced GH release. In 6 normal male volunteers (aged 22-27 yr) we studied the interaction of the maximally effective iv dose of Hexarelin (HEX, 2 micrograms/kg iv at 0 min) with atenolol (100 mg po at -60 min) or salbutamol (0.08 mg/kg po at -60 min), which are beta-adrenergic antagonist and agonist, respectively. HEX induced a marked GH rise (AUC, mean +/- SE: 4573.2 +/- 588.8 micrograms.min/L), which was unchanged by atenolol (4706.2 +/- 928.2 micrograms.min/L) but blunted by salbutamol (2792.8 +/- 618.0 micrograms.min/L, p < 0.03). In conclusion, present data show that, in man, the GH-releasing effect of Hexarelin is not enhanced by beta-adrenergic blockade while is only blunted by the activation of beta receptors. According to other data, these results indicate that the potent GH-releasing activity of Hexarelin is, at least partially, refractory to beta-adrenergic-mediated manipulations of somatostatinergic activity.

Beta‐adrenergic agonism does not impair the GH response to acylated ghrelin in humans

“…Ghrelin itself is likely to represent a good provocative test to evaluate somatotroph function. As a GH‐releasing stimulus, AG has been shown to be more potent than synthetic GHS 12 and even less sensitive than synthetic GHS to the inhibitory effect of somatostatin and metabolic fuels such as glucose and FFA, 8,11,13,14 and, according to the present data, even to SLB 6 …”

“…The results of this study show that the potent GH‐releasing effect exerted by the intravenous administration of AG is not modified by the SLB‐induced pharmacological activation of beta‐adrenergic receptors. These findings indicate that, in humans, the GH‐releasing effect of AG is refractory to the modulation by the beta‐adrenergic system, which, on the contrary, is known to abolish the GH response to GHRH and even to blunt that to hexarelin, a synthetic peptidyl GHS 1,6,7 …”

“…It is well known that the activity of the somatotroph axis is profoundly modulated by the adrenergic system, acting directly at the hypothalamus/pituitary level and also peripherally influencing glucose and lipid metabolism 1 . In humans, beta‐adrenergic antagonists have been shown to potentate the GH response to GHRH but to abolish the GHRH‐induced GH rise and blunt the GH response to hexarelin 1,6 . The role, if any, of beta‐adrenergic receptor activation in the modulation of the somatotroph response to ghrelin administration has not previously been investigated.…”

Interaction of the growth hormone releasing peptide hexarelin with somatostatin

“…Indeed, the GH-releasing activity of GHRPs seems refractory to a number of inhibitory influences which are thought to inhibit GH secretion by stimulating endogenous SS release. These include pharmacological manipulations such as the administration of the muscarinic antagonist pirenzepine or the b2-adrenergic agonist salbutamol (Arvat et al, 1996), and metabolic manipulations such glucose or lipid administration (Maccario et al, 1995).…”

Endocrine and Non-Endocrine Activities of Growth Hormone Secretagogues in Humans

“…In fact, in humans the GH response to GHS is not modified by substances acting via somatostatin inhibition (such as cholinergic agonists, arginine) which, in turn, truly potentiate the GHRH-induced GH rise [2, 30, 31]. Moreover, the GH releasing activity of GHS is partially refractory to the inhibitory effect of substances acting via stimulation of hypothalamic somatostatin (such as cholinergic antagonists, beta-adrenergic agonists, glucose) which, in turn, almost abolish the somatotroph responsiveness to GHRH [2, 30, 31, 32, 33]. Above all, GHS are also partially refractory to the inhibitory effect of substances acting on somatotroph cells such as free fatty acids and even to exogenous somatostatin [31, 33, 34].…”