Nocturnal growth hormone (GH) secretion is eliminated by infusion of GH-releasing hormone antagonist.
The neuroendocrine mechanisms underlying the generation of pulsatile GH secretion in humans are poorly understood. GH secretory pulses are likely to result from acute GHRH secretory episodes, acute decreases in hypothalamic somatostatin secretion, or a combination of these mechanisms. In earlier studies we demonstrated that a single i.v. bolus of a competitive GHRH antagonist [N-Ac-Tyr1,D-Arg2)GHRH-(1-29); GHRH-Ant] blocked 40% of the nocturnal GH release. Failure to more completely eliminate nocturnal GH secretion could be due to either incomplete antagonism of endogenous GHRH action by GHRH-Ant or a non-GHRH component of GH release. We subsequently investigated whether a continuous infusion of GHRH-Ant would more completely eliminate nocturnal GH secretion. Eight men were given a 400 micrograms/kg i.v. bolus of GHRH-Ant at 2300 h, followed by a 50 micrograms/kg.h i.v. infusion of GHRH-Ant between 2300-0700 h or a saline bolus followed by a saline infusion. An i.v. bolus of GHRH (1 microgram/kg) was given at 0500 h on both occasions. Blood was sampled every 10 min between 2300-0700 h. As measured by the area under the curve (AUC) from 2400-0500 h, GHRH-Ant suppressed GH secretion by an average of 89% (1795 +/- 412 vs. 164 +/- 46 micrograms/min.L; P = 0.004). The response to GHRH was suppressed by 79% (484 +/- 140 vs. 64 +/- 19 micrograms/min.L; P = 0.02). These data demonstrate that the previously observed nonsuppressible GH secretion was probably due to incomplete blockade of pituitary GHRH receptors and that all or nearly all of nocturnal GH pulsatility can be attributed to the effect of hypothalamic GHRH.
Ocampo-Lim
B
B
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA.
Guo
W
W
DeMott-Friberg
R
R
Barkan
A L
AL
Jaffe
C A
CA
D000293:Adolescent; D000328:Adult; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013997:Time Factors
D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone