Twenty-four-hour growth hormone (GH)-releasing peptide (GHRP) infusion enhances pulsatile GH secretion and specifically attenuates the response to a subsequent GHRP bolus.

Abstract

GH-releasing peptide (GHRP; SK&F 110679) is a synthetic hexapeptide that specifically stimulates GH release through nonopiate non-GH-releasing hormone (non-GHRH) receptors. To determine the effects of a 24-h GHRP infusion, eight normal young men received infusions of saline for 2 h, then saline (on two occasions) or GHRP (1.0 micrograms/kg.h; on two occasions) for 24 h, followed by an iv bolus of GHRP or GHRH (1.0 micrograms/kg) and a 2.5-h saline infusion. Serum GH was measured every 10 min throughout the 28.5-h period. GH secretion rates [per L distribution volume (Lv)] were determined by deconvolution analysis; attributes of pulsatile GH release were assessed by Cluster analysis. GH secretion was enhanced and remained pulsatile during GHRP infusions. The two GHRP infusions increased GH secretion rates (micrograms per Lv/h) 8-fold compared to saline (GHRP, 12 +/- 2.1 and 12 +/- 2.2; saline, 1.5 +/- 0.34 and 1.4 +/- 0.27; P < 0.05). The number of GH pulses, pulse duration and height, incremental pulse amplitude, interpeak valley concentration, and individual pulse areas were significantly greater during GHRP infusions than during saline treatment. Attributes of pulsatile GH release on the two GHRP infusion days were significantly correlated, indicating that enhancement of GH secretion by GHRP is highly reproducible. Mean plasma insulin-like growth factor-I (IGF-I) concentrations increased 12% and 22% on GHRP infusion days, whereas IGF-I levels declined 18% and 20% during saline infusions (P < 0.05). GHRP infusion significantly attenuated the GH response to a subsequent GHRP bolus injection; both GH secretion rates (GHRP, 4.1 +/- 1.6; saline, 19 +/- 3.0 micrograms/Lv.h; P < 0.05) and peak GH concentrations (GHRP, 7.9 +/- 2.9; saline, 25 +/- 2.9 micrograms/L; P < 0.05) were decreased. In contrast, peak GH concentrations in response to GHRH were significantly increased after GHRP infusion compared to those after saline treatment (24 +/- 4.7 vs. 11 +/- 2.7 micrograms/L; P < 0.05). We conclude that 24-h GHRP infusions augment pulsatile GH release and increase plasma IGF-I concentrations without significant adverse effects. Attenuation of the GH response to a subsequent GHRP bolus is not caused by depletion of pituitary GH, since the response to a GHRH bolus was enhanced by prior infusion of GHRP.