This study makes me think we might be overcomplicating matters with multiple peptides.
Pulsatile Secretion of Growth Hormone (GH) Persists
during Continuous Stimulation by CJC-1295, a LongActing GH-Releasing Hormone Analog
Madalina Ionescu and Lawrence A. Frohman
Section of Endocrinology, Metabolism, and Diabetes, University of Illinois at Chicago, Chicago, Illinois 60608
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 g/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
enhan***ent of trough GH levels by continuous GHRH stimulation
implicates the importance of this effect on increasing IGF-I. Longacting GHRH preparations may have clinical utility in patients with
intact pituitary GH secretory capability. (J Clin Endocrinol Metab
91: 4792– 4797, 2006)