The decrease in growth hormone (GH) response after repeated stimulation with GH-releasing hormone is partly caused by an elevation of somatostatin tonus.

Repeated injection of GHRH leads to a decrease in the GH response in normal subjects. Arginine (Arg) stimulates GH secretion by suppression of hypothalamic somatostatin. To confirm these findings, eight normal men were examined in a series of five settings: test 1 (GHRH/GHRH-TRH), 100 micrograms GHRH injected iv, followed by 100 micrograms GHRH, iv, after 120 min and 200 micrograms TRH, iv, after 150 min; test 2 (GHRH/Arg-TRH), like test 1, but instead of the second GHRH injection, a 30 g Arg infusion over 30 min; test 3 (GHRH/GHRH-Arg-TRH), like test 1, but additionally a 30 g Arg infusion after 120 min; test 4 (GHRH-Arg-TRH), iv GHRH and Arg infusion initially, followed by iv TRH after 30 min; and test 5 (TRH), 200 micrograms TRH, iv, at 0 min. For statistical evaluation, the area under the GH curve (AUC) from 0-120 min was compared with the AUC from 120-240 min. The GH response to the second administration of GHRH was significantly lower (P < 0.02) than the first increase [AUC, 0.5 +/- 0.01 min.mg/L (mean +/- SE) vs. 1.2 +/- 0.3]. No significant differences were found between the GH responses to either GHRH or Arg alone (AUC, 0.9 +/- 0.2 min.mg/L vs. 0.9 +/- 0.2). A larger GH increase (P < 0.02) was seen after GHRH-Arg compared to GHRH alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 1.2 +/- 0.3). The GH response (P < 0.02) to GHRH-Arg stimulation was lower after previous GHRH injection than after GHRH-Arg stimulation alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 3.5 +/- 0.9). There was a statistically significant difference between the TRH-stimulated TSH response in test 4 compared to that in test 5. We could show that decreasing GH responses to repeated GHRH can be avoided by a combined stimulation with GHRH/Arg. These findings suggest that the decreased GH response to a second GHRH bolus may be partly due to an elevated hypothalamic somatostatin secretion, which can be suppressed by Arg. The lower GH response to GHRH-Arg stimulation after a previous GHRH bolus suggests, furthermore, that the readily available GH pool in the human pituitary may be limited.