IN OBESITY THE SOMATOTROPE RESPONSE TO EITHER GROWTH HORMONE-RELEASING HORMONE OR ARGININE IS INHIBITED BY SOMATOSTATIN OR PIRENZEPINE BUT NOT BY GLUCOSE

It is known that spontaneous and stimulated GH secretion is reduced in obesity. On the other hand, it has been recently reported that, in ob ese subjects, plasma GH levels did not change during a hyperglycemic c lamp. To further study the sensitivity of somatotrope cells to inhibit ory influences in obesity, we studied the effect of somatostatin, pire nzepine, or glucose on the GH response to GHRH or arginine in 32 obese patients and 30 controls. Basal GH levels were lower in obese than in normal subjects (1.0 +/- 0.6 vs. 4.8 +/- 0.7 mu g/L, P < 0.05), while insulin-like growth factor-I levels were similar in both groups (137. 3 +/- 13.2 us. 138.8 +/- 12.2 mu g/L). In obese as well as in control subjects pirenzepine abolished the GH response to either GHRH (AUC(0-1 20): 43.7 +/- 9.6 vs. 258.3 +/- 59.9 mu g/L/h, P < 0.04 and 113.0 +/- 75.0 vs. 870.5 +/- 255 mu g/L . h, P < 0.01, respectively) or arginine (6.5 +/- 2.5 vs. 118.7 +/- 55.9 mu g/L . h, P < 0.05 and 47.7 +/- 7.3 vs. 334.0 +/- 157.5 mu g/L . h, P < 0.01, respectively). Differently from pirenzepine, glucose blunted the GH response to either GHRH or ar ginine in control subjects (260.8 +/- 38.3 us. 479.5 +/- 83.9 mu g/L . h, P < 0.03 and 294.8 +/- 46.3 vs. 625.1 +/- 139.1 mu g/L . h, P < 0. 05, respectively), but failed to modify it in obese patients (193.7 +/ - 39.4 vs. 172.4 +/- 33.6 mu g/L . h and 121.1 +/- 43.4 vs. 155.1 +/- 39.7 mu g/L . h, respectively). On the other hand, somatostatin deeply blunted the GHRH-induced GH release in obese patients (58.5 +/- 25.4 us. 548.7 +/- 196.6 mu g/L . h, P < 0.05) as well as in controls (181. 4 +/- 44.4 us. 759.7 +/- 46.6 mu g/L . h, P < 0.04). In conclusion, ou r results show that, in obesity, the stimulated GH release is refracto ry to the inhibitory effect of glucose but not of pirenzepine, in spit e of their likely common mechanism of action, i.e. increase of hypotha lamic somatostatin release. Exogenous somatostatin is able to abolish GH secretion both in normal and obese subjects. These data suggest the existence of a peculiar inhability of hyperglycemia to trigger somato statinergic release in obesity.