The inhibitory effects of growth hormone-releasing hormone (GHRH)-antagonist on GHRH, L-dopa, and clonidine-induced GH secretion in normal subjects

The relative inhibitory potency of GHRH-Antagonist (GHRH-Ant) to GHRH(1-44)NH2 and mechanism of L-dopa- or clonidine-induced GH release were studied in seven normal subjects using GHRH-Ant. One hundred micrograms of GHRH-Ant (iv for 75 min) did not inhibit plasma GK responses to bolus injection of 100 mu g and 10 mu g GHRH or simultaneous infusion of 5 mu g GHRH (iv for 75 min). However, 200 mu g GHRH-Ant (iv for 75 min) significantly inhibited GK release, which was induced by simultaneous infusion of 5 mu g GHRH. Although 100 mu g GHRH-Ant could not significantly inhibit L-dopa-induced GH release, 200 mu g GHRH-Ant almost completely inhibited the response. Similarly, the same dose of GHRH-Ant markedly inhibited the GH-releasing activity of clonidine. It is concluded that the inhibitory potency of GHRH-Ant on GHRH(1-44)NH2 is relatively weak (about 1/60 in molar base), and that L-dopa- or clonidine-induced GH release seems to be mediated by the release of hypothalamic GHRH.