Effects of a prolonged growth hormone (GH)-releasing peptide infusion on pulsatile GH secretion in normal men.

Abstract

Bolus injection of the synthetic hexapeptide GH-releasing peptide-6 (GHRP-6) reliably promotes GH secretion. However, desensitization to the GH-releasing effects of GHRP has been shown to occur during short term iv infusion. To determine whether humans would remain responsive to prolonged exposure to GHRP and to study the mechanism of action of GHRP, we compared the effects of a 34-h iv infusion of either GHRP or normal saline on parameters of pulsatile GH concentration in nine healthy young men. Each infusion was administered from 0800 h on day 1 to 1800 h on day 2. GHRP was given as a 1 microgram/kg loading bolus, then at the rate of 1 microgram/kg.h. A 50-microgram iv bolus of TRH was given at 0800 h on day 2, followed by iv boluses of GH-releasing hormone (GHRH; 1 microgram/kg, iv, at 1000, 1200, and 1400 h) and then a bolus of GHRP (1 microgram/kg at 1600 h). The integrated GH concentration (IGHC) and parameters of pulsatile GH concentration were calculated for the period between 1400 h on day 1 to 0800 h on day 2, and IGHC was calculated for 2 h after each bolus of GHRP or GHRH. During GHRP infusion, there was a significant increase in IGHC (2908 +/- 450 vs. 1374 +/- 160 micrograms x min/L), maximum pulse amplitude (15.2 +/- 2.8 vs. 8.4 +/- 1.7 micrograms/L), and mean pulse amplitude (7.0 +/- 1.1 vs. 3.8 +/- 1.5 micrograms/L). Plasma insulin-like growth factor-I increased from 252 +/- 23 to 312 +/- 23 micrograms/L. There was no change in either GH pulse frequency or interpulse GH concentration. During GHRP infusion, the GH responses to the GHRH boluses were augmented; however, baseline TSH was lower, and the GH and TSH/PRL responses to GHRP and TRH, respectively, were smaller. We conclude that the pituitary remains sensitive to GHRP during a prolonged GHRP infusion. The mechanisms of the GHRP effect on GH secretion are uncertain, and the possibility that GHRP acts as a functional somatostatin antagonist is discussed. The contrasting effects of GHRP on GH and TSH/PRL secretion could be due to differential effects of GHRP on the pituitary and hypothalamus.

Involvement of Nitric Oxide in the Regulation of Growth Hormone Secretion in Dogs

“…Since both peptides were administered at a maximal effective dose their marked synergistic effects are unlikely to be mediated by increased hypothalamic GHRH and/or Ghrelin release [30, 32, 33, 34, 35, 36]. When L-NAME was administered in combination with both peptides, it reduced these synergistic effects.…”

Chronic Central Infusion of Growth Hormone Secretagogues: Effects on Fos Expression and Peptide Gene Expression in the Rat Arcuate Nucleus

“…At the pituitary level the desensitisation caused by GH secretagogues appears to be reserved, at least to some extent, by somatostatin, resulting in periods of resensitisation [19]. This mechanism may explain why, in man, pulsatile GH secretion continues during chronic exposure to GH secretagogues [16, 17], particularly if analogous mechanisms operate centrally. To confirm that pulsatile GH secretion does persist during chronic central GH secretagogue infusion it would be necessary to perform continual blood sampling over the infusion period.…”

“…injections of GH secretagogues is variable [13, 14], in a similar manner to that described for repeated GHRH injections [15]. However, continuous infusions of GH secretagogues have been reported to amplify GH secretion and pulsatility [16, 17, 18]. In man, systemic GHRP-6 infusion attenuates the GH response to a subsequent bolus injection of GHRP-6 [16, 18].…”

Growth Hormone Secretagogues in Critical Illness

“…3) [8, 9]. The responses to GHRP-2 infusion in these critically ill patients were pronounced compared with the responses to GHRP-6 and to GHRH infusion reported in healthy volunteers [36, 37, 38]. These high responses to the continuous infusion of hypothalamic releasing factors further support a hypothalamic origin of the relative hyposomatotropism in the chronic phase of critical illness.…”