Growth hormone-releasing peptide-2 stimulates GH secretion in GH-deficientpatients with mutated GH-releasing hormone receptor

GH-releasing peptides (GHRPs) are synthetic peptides that bind to specific receptors and thereby stimulate the secretion of pituitary GH. In vivo it i s uncertain whether these peptides act directly on somatotroph cells or ind irectly via release of GHRH from the hypothalamus. In this study we compare d the pituitary hormone response to GHRP-2 in 11 individuals with isolated GH deficiency (GHD) due to a homozygous mutation of the GHRH receptor (GHRH -R) gene and in 8 normal unrelated controls. Basal serum GH levels were lower in the GHD group compared with controls [0 .11 +/- 0.11 (range, <0.04 to 0.38) vs. 0.59 +/- 0.76 mug/L (range, 0.04-2. 12 mug/L); P = 0.052]. After GHRP-2 administration there was a 4.5-fold inc rease in serum GH relative to baseline values in the GHD group (0.49 +/- 0. 41 vs. 0.11 +/- 0.11 mug/L; P = 0.002), which was significantly less than t he 79-fold increase in the control group (46.8 +/- 17.6 vs. 0.59 +/- 0.76 m ug/L; P = 0.008). Basal and post-GHRP-2 serum levels of ACTH, cortisol, and PRL were similar in both groups. Basal levels of serum TSH were significan tly higher in the GHD group than in the control group (3.23 +/- 2.21 vs. 1. 37 +/- 0.34 mu IU/mL; P = 0.003). TSH levels in both groups did not change after GHRP-2 administration. These results suggest that an intact GHRH signaling system is not an absolu te requirement for GHRP-2 action on GH secretion and that GHRP-2 has a GHRH -independent effect on pituitary somatotroph cells.