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.
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