The somatotropic axis in critical illness: Effect of continuous growth hormone (GH)-releasing hormone and GH-releasing peptide-2 infusion

Greet Van Den Berghe, Francis De Zegher, Johannes D Veldhuis, Pieter Wouters, Mariet Awouters, Werner Verbruggen, Miet Schetz, Charles Verwaest, Peter Lauwers, Roger Bouillon, Cyril Y. Bowers

Research output: Contribution to journalArticle

124 Scopus citations


Prolonged critical illness is characterized by protein hypercatabolism and preservation of fat depots, associated with blunted GH secretion, elevated serum cortisol levels, and low insulin-like growth factor I (IGF-I) concentrations. In this condition, GH is readily released in response to a bolus of GHRH and GH-releasing peptide-2 (GHRP-2) and, paradoxically, to TRH. We further explored the altered somatotropic axis and cortisol secretion in critical illness by examining the effects of continuous GHRH and/or GHRP-2 infusion. Twenty-six critically ill adults (mean age ± SEM, 63 ± 2 yr) were studied during 2 consecutive nights (2100-0600 h). According to a weighed randomization, they received one of four combinations of infusions within a randomized cross-over design for each combination: placebo (one night) and GHRP-2 (the other night; n = 10), placebo and GHRH (n = 4), GHRH and GHRP-2 (n = 6), and GHRP-2 and GHRH plus GHRP-2 (n = 6). The peptide infusions (duration, 21 h) were started after a bolus of 1 μg/kg at 0900 h and infused (1 μg/kg/h) until 0600 h. Serum concentrations of GH were determined every 20 min, cortisol every hour, and IGF-I at 2100 and 0600 h on each study night. The placebo profiles showed pulsatile GH secretion with low secretory burst amplitude [0.062 ± 0.008 μg/L distribution volume (L(v)l/min], high burst frequency (6.6 ± 0.4 events/9 h), and detectable basal secretion (0.041 ± 0.009 μg/L(v)/min) in the face of low serum IGF-I (106 ± 11 μg/L). IGF-I correlated positively and significantly with the basal component, the pulsatile component, and the total amount of nightly GH secretion. GHRH elicited a 2- to 3-fold increase in the mean GH concentration (P = 0.006), the GH secretory burst amplitude (P = 0.007), and basal GH secretion (P = 0.03). GHRP-2 provoked a 4- to 6-fold increase in the mean GH concentration (P < 0.0001), the GH secretory burst amplitude (P = 0.002), and basal GH secretion (P = 0.0007), which were associated with a 61 ± 13% increase in serum IGF-I within 24 h (P = 0.02). Compared to GHRP-2 alone, GHRH plus GHRP-2 elicited a further 2-fold increase in the mean GH concentration (P = 0.04) and GH basal secretion (P = 0.02), and an additional 40 ± 6% rise in serum IGF-I (P = 0.04). GHRH and GHRP-2 infusion did not alter elevated cortisol levels. In critically ill adults, low serum IGF-I levels were positively correlated with diminished pulsatile and increased basal GH secretion. Both basal and pulsatile GH secretion were moderately increased by continuous infusion of GHRH, substantially increased by GHRP-2, and strikingly increased by GHRH plus GHRP-2. GHRP-2 alone or combined with GHRH elicited a robust rise in circulating IGF-I levels within 24 h without altering serum cortisol levels. These findings open perspectives for GH secretagognes as potential antagonists of the catabolic state in critical care medicine.

Original languageEnglish (US)
Pages (from-to)590-599
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'The somatotropic axis in critical illness: Effect of continuous growth hormone (GH)-releasing hormone and GH-releasing peptide-2 infusion'. Together they form a unique fingerprint.

  • Cite this

    Van Den Berghe, G., De Zegher, F., Veldhuis, J. D., Wouters, P., Awouters, M., Verbruggen, W., Schetz, M., Verwaest, C., Lauwers, P., Bouillon, R., & Bowers, C. Y. (1997). The somatotropic axis in critical illness: Effect of continuous growth hormone (GH)-releasing hormone and GH-releasing peptide-2 infusion. Journal of Clinical Endocrinology and Metabolism, 82(2), 590-599.