Inhibition by Gastrin-Releasing Peptide of Growth Hormone (GH) Secretion Induced by Human Pancreatic GH-Releasing Factor in Rats*

Intravenous injection of synthetic human pancreatic GH-releasing factor (1-44) [hpGRF(1-44)] (50 ng-1 micrograms/100 g BW) resulted in a dose-related increase in plasma GH levels in urethane-anesthetized male rats. Pretreatment with cysteamine (30 mg/100 g BW, sc, 4 h previously) or anti-SRIF rabbit serum (0.5 ml/rat, iv, 1 h previously) raised basal plasma GH levels and markedly exaggerated the plasma GH response to hpGRF (1-44) (80 ng/100 g BW, iv). The intraventricular injection of gastrin-releasing peptide (GRP) (1 micrograms/rat) completely inhibited the increase of plasma GH induced by hpGRF (80 ng/100 g BW, iv) in control rats. However, in the rats treated with cysteamine or anti-SRIF rabbit serum, the inhibitory effect of GRP on hpGRF-induced GH release was significantly attenuated. hpGRF (10(-11)-10(-8) M) stimulated in a dose-related manner GH release from rat anterior pituitary cells superfused in vitro. GRP (10(-5) M) did not affect pituitary GH release induced by hpGRF (10(-9) M) in vitro. These results indicate that hpGRF stimulates rat GH secretion by acting at the pituitary level and the hypothalamic SRIF interacts with the action of GRF, and that GRP inhibits GH secretion, at least in part, by stimulating SRIF release from the hypothalamus.