Effects of alpha- and Beta-adrenergic agonists and antagonists on growth hormone secretion in man

Abstract It is well known that the adrenergic system has both stimulatory and inhibitory influences on growth hormone (GH) secretion probably by modulating GH-releasing hormone (GHRH) and/or somatostatin release. To better understand the mechanisms by which these influences take place, we investigated the effects of alpha- and beta-adrenergic agonists and antagonists on both basal and GHRH-induced GH release in 23 male adult volunteers. The GH-releasing effect of clonidine (0.15 mg infused iv over 10 min), an alpha(2)-adrenergic agonist, was significantly blunted by yohimbine (30 mg orally at -50 min), a relatively specific alpha(2)-adrenergic antagonist area under the response curve, mean+/-SEM: 672.6 +/- 143.0 versus 219.6 +/- 16.7 mug/l/h; P<0.05). On the other hand, the GHRH (1 mug/kg iv as a bolus)-induced GH increase was unaffected by yohimbine (339.3 +/- 19.1 versus 518.1+/-172.8 mug/I/h). Concomitant blockade of alpha(1)-/alpha(2)-adrenoreceptors by phentolamine (0.5 mg/ml/min infused iv from -60 to +30 min) abolished the GHRH-induced GH rise (645.5+/- 106.0 versus 189.0+/-58.8 mug/l/h; P<0.01). Finally, the GHRH-stimulated release was blunted by beta(2)-adrenergic stimulation with salbutamol (10 mug/min infused iv from -5 to +15 min) (324.3 +/- 99.7 versus 112.7 +/- 48.8 mug/l/h; P<0.02).

1) The evidence that yohimbine is able to blunt the clonidine-induced GH release but fails to inhibit the GHRH-induced GH rise indicates that, as in animals, in man too the GH-releasing effect of clonidine is specifically mediated by alpha(2)-receptor activation, and may occur via endogenous GHRH release; 2) the inhibitory effect on GH release of beta, namely beta(2), receptor activation is probably mediated by the somatostatinergic system; 3) an unopposed beta-adrenergic activation would account for the inhibitory effect on GHRH-induced GH release of concomitant alpha(1)-/alpha(2)-adrenoreceptor blockade by phentolamine.