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Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog

Section of Endocrinology, Metabolism, and Diabetes, University of Illinois at Chicago, Chicago, Illinois 60608

Address all correspondence and reprint requests to: Lawrence A. Frohman, M.D., University of Illinois at Chicago, Section of Endocrinology, Metabolism, and Diabetes, 1747 West Roosevelt Road, Room 517, Chicago, Illinois 60608. E-mail: Frohman{at}uic.edu.

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

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

Methods: GH pulsatility was assessed by 20-min blood sampling during an overnight 12-h period in healthy 20- to 40-yr-old men before and 1 wk 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 were 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-I levels (45%; P < 0.001). No significant differences were observed between the responses to the two drug doses. The IGF-I increases did not correlate with any parameters of GH secretion.

Conclusions: CJC-1295 increased trough and mean GH secretion and IGF-I 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-I. Long-acting GHRH preparations may have clinical utility in patients with intact pituitary GH secretory capability.