Context: Pulsatile GH secretion is considered important for many of the hormone's physiologic effects. Short-term GHRH infusions enhance GH pulsatility and increase IGF-1, but the short GHRH half-life limits its therapeutic use. A synthetic GHRH analog (CJC-1295) that binds permanently to endogenous albumin after injection (t1/2 = 8 d) stimulates GH and IGF-1 secretion in several animal species and in normal human subjects and enhances growth in rats.

Objective: To assess GH pulsatility after a single injection of CJC-1295 and determine which GH secretion parameters correlated to the increase in IGF-1 production.

Methods: GH pulsatility was assessed by 20-minute blood sampling during an overnight 12 h period in healthy 20-40 yr old men before and one week after injection of either 60 or 90 µg/kg CJC-1295.

Results: GH secretion was increased after CJC-1295 administration with preserved pulsatility. The frequency and magnitude of GH secretory pulses were unaltered. However, basal (trough) GH levels was markedly increased (7.5 fold; P < 0.0001) and contributed to an overall increase in GH secretion (mean GH levels: 46%; P < 0.01) and IGF-1 levels (45%; P < 0.001). No significant differences were observed between the responses to the two drug doses. The IGF-1 increases did not correlate with any parameters of GH secretion.

Conclusions: CJC-1295 increased trough and mean GH secretion and IGF-1 production with preserved GH pulsatility. The marked enhancement of trough GH levels by continuous GHRH stimulation implicates the importance of this effect on increasing IGF-1. Long-acting GHRH preparations may have clinical utility in patients with intact pituitary GH secretory capability.