GLUCAGON STIMULATES GH SECRETION AFTER INTRAMUSCULAR BUT NOT INTRAVENOUS ADMINISTRATION - EVIDENCE AGAINST THE ASSUMPTION THAT GLUCAGON PERSE HAS A GH-RELEASING ACTIVITY

In order to verify the true GH-releasing effect of glucagon and to exp lain the mechanism underlying this effect, we studied the effect of gl ucagon (GLU, 1 mg) administered either iv or im on both basal and GHRH (1 mu g/kg)-induced GH rise in 48 normal short children and adolescen ts, Moreover, the in vitro effect of GLU on rat anterior pituitary cel ls was studied. Intravenous administration of GLU induced no significa nt GH rise. On the other hand, im GLU administration induced a clearcu t GH increase (mean +/- SE GH peak after GLU vs placebo = 25.7+/-3.9 v s 1O.1+/-3.6 mu g/L, p<0.01). Intravenous administration of GLU failed to modify the GHRH-induced GH rise either when coadministered with th e neurohormone (35.2+/-4.1 vs 34.1+/-6.0 mu g/L) or when given 60 min earlier (20.2+/-5.8 vs 21.1+/-8.3 mu g/L). Differently from iv GLU, im GLU strikingly potentiated the GH response to GHRH given 90 min later (57.5+/-6.3 vs 24.7+/-9.1 mu g/L, p<0.01). Mean plasma glucose levels increased 30 min after GLU, administered either iv or im, and returne d to basal levels 60 min later. GH secretion from dispersed rat pituit ary cells was unaffected by incubation with GLU (10(-10)-10(-4) mol/L) . Incubation of the cells with 10(-7) mol/L GHRH induced instead a cle ar-cut stimulation of GH release. In conclusion, our data demonstrate that glucagon per se has not GH-releasing activity as indicated by its uneffectiveness to release GH in vitro and after intravenous administ ration. The mechanisms underlying the GH increase which follows intram uscular administration of glucagon are not clear.