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 microgra ms 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 simultan eous infusion of 5 mu g GHRH. Although 100 mu g GHRH-Ant could not sig nificantly inhibit L-dopa-induced GH release, 200 mu g GHRH-Ant almost completely inhibited the response. Similarly, the same dose of GHRH-A nt markedly inhibited the GH-releasing activity of clonidine. It is co ncluded that the inhibitory potency of GHRH-Ant on GHRH(1-44)NH2 is re latively weak (about 1/60 in molar base), and that L-dopa- or clonidin e-induced GH release seems to be mediated by the release of hypothalam ic GHRH.