Enhancement of pulsatile growth hormone secretion by continuous infusion of a growth hormone-releasing peptide mimetic, L-692,429, in older adults--a clinical research center study.

Abstract

L-692,429 ([L]) is a GH-releasing peptide mimetic that stimulates GH secretion when administered acutely. To determine the effect of its continuous administration, six older adults (four men and two women, aged 64-82 yr) received i.v. transfusions of 1) saline for 24 h (control), 2) [L] (0.05 mg/kg.h) for 24 h (low dose), and 3) [L] (0.1 mg/kg.h) for 12 h, then saline for 12 h (high dose), followed on all admissions by saline for 2.5 h. GHRH (1 microgram/kg, i.v.) was given 30 min before the end of each 24-h treatment. Blood was collected every 10 min for GH measurement, and GH secretion was assessed by deconvolution analysis. Pulsatile GH secretion continued throughout both [L] infusions. During the first 12 h (when comparison of both doses was possible), [L] exerted a dose-dependent stimulatory effect on mean GH concentrations, from 0.6 +/- 0.1 (control, mean +/- SE), to 1.2 +/- 0.2 (low dose [L]) and 2.3 +/- 0.5 microgram/L (high dose [L]; P < 0.05, high dose vs. control), and on calculated GH secretory rates [1.6 +/- 0.3 (control), 2.5 +/- 0.3 (low dose [L]), and 5.8 +/- 0.7 microgram/L distribution vol.h (high dose [L]); P < 0.05, high dose vs. control]. GH secretory pulse height and area increased significantly in a dose-responsive manner, without significant changes in GH secretory pulse number, half-duration of pulses, or GH half-life. GH concentrations remained elevated during the second 11.5 h of low dose [L] infusion. Over the 23.5-h period before GHRH administration, mean GH concentrations and secretion rates were significantly higher than control values with high dose, but not low dose, [L]. Low dose [L] enhanced the peak GH response to GHRH (17.4 +/- 3.5 micrograms/L) compared to the control value (8.4 +/- 2.8 micrograms/L; P < 0.05). We conclude that the administration of [L] to healthy older adults by continuous i.v. infusion enhances pulsatile GH secretion by increasing the mass of GH secreted per pulse, but not the number of secretion pulses, and increases the GH response to GHRH.