Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness

Objective: During prolonged critical illness, nocturnal pulsatile secretion of GH, TSH and prolactin (PRL) is uniformly reduced but remains responsive to the continuous infusion of GH secretagogues and TRH. Whether such (pertinent) secretagogues would synchronize pituitary secretion of GH, TSH and/or PRL is not known. Design and methods: We explored temporal coupling among GH, TSH and PRL release by calculating cross-correlation among GH, TSH and PRL serum concentration profiles in 86 time series obtained from prolonged critically ill patients by nocturnal blood sampling every 20 min for 9 h during 21-h infusions of either placebo (n = 22), GHRH (1 μg/kg/h; n = 10), GH-releasing peptide-2 (GHRP-2; 1 μg/kg/h; n = 28), TRH (1 μg/kg/h; n = 8) or combinations of these agonists (n = 18). Results: The normal synchrony among GH, TSH and PRL was absent during placebo delivery. Infusion of GHRP-2, but not GHRH or TRH, markedly synchronized serum profiles of GH, TSH and PRL (all P≤0.007). After addition of GHRH and TRH to the infusion of GHRP-2, only the synchrony between GH and PRL was maintained (P=0.003 for GHRH+GHRP-2 and P=0.006 for TRH + GHRH + GHRP-2), and was more marked than with GHRP-2 infusion alone (P = 0.0006 by ANOVA). Conclusions: The nocturnal GH, TSH and PRL secretory patterns during prolonged critical illness are herewith further characterized to include loss of synchrony among GH, TSH and PRL release. The synchronizing effect of an exogenous GHRP-2 drive, but not of GHRH or TRH, suggests that the presumed endogenous GHRP-like ligand may participate in the orchestration of coordinated anterior pituitary hormone release.