INFLUENCE OF BETA-ADRENERGIC AGONISTS AND ANTAGONISTS ON THE GH-RELEASING EFFECT OF HEXARELIN IN MAN

Beta-adrenergic receptors mediate the inhibitory influence of cathecol amines on GH secretion, probably via the stimulation of hypothalamic s omatostatin release. Accordingly, beta-adrenergic agonists and antagon ists inhibit and increase, respectively, the GH response to many stimu li, 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 Hexare lin, a synthetic GH-releasing hexapeptide. Interestingly, the OH-relea sing effect of Hexarelin has been reported to be partially refractory to neuroendocrine manipulations known to strongly enhance or abolish t he GHRH-induced GH release. In 6 normal male volunteers (aged 22-27 yr ) we studied the interaction of the maximally effective iv dose of Hex arelin (HEX, 2 mu g/kg iv at 0 min) with atenolol (100 mg po at -60 mi n) or salbutamol (0.08 mg/kg po at -60 min), which are beta-adrenergic antagonist and agonist, respectively. HEX induced a marked GH rise (A UG, mean+/-SE: 4573.2+/-588.8 mu g.min/L), which was unchanged by aten olol (4706.2+/-928.2 mu g.min/L) but blunted by salbutamol (2792.8+/-6 18.0 mu g.min/L, p<0.03). In conclusion, present data show that, in ma n, the OH-releasing effect of Hexarelin is not enhanced by beta-adrene rgic blockade while is only blunted by the activation of beta receptor s. According to other data, these results indicate that the potent OH- releasing activity of Hexarelin is; at least partially, refractory to beta-adrenergic-mediated manipulations of somatostatinergic activity.