Growth hormone-releasing peptide-2 stimulates GH secretion in GH-deficient patients 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 is uncertain whether these peptides act directly on somatotroph cells or indirectly via release of GHRH from the hypothalamus. In this study we compared 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 microg/L (range, 0.04-2.12 microg/L); P = 0.052]. After GHRP-2 administration there was a 4.5-fold increase in serum GH relative to baseline values in the GHD group (0.49 +/- 0.41 vs. 0.11 +/- 0.11 microg/L; P = 0.002), which was significantly less than the 79-fold increase in the control group (46.8 +/- 17.6 vs. 0.59 +/- 0.76 microg/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 significantly higher in the GHD group than in the control group (3.23 +/- 2.21 vs. 1.37 +/- 0.34 microIU/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 absolute requirement for GHRP-2 action on GH secretion and that GHRP-2 has a GHRH-independent effect on pituitary somatotroph cells.
Gondo
R G
RG
Endocrine-Genetics Unit/LIM 25, Department of Medicine, University of Sao Paulo School of Medicine, 01246-903 Sao Paulo, Brazil. gondo_rog@hotmail.com
Aguiar-Oliveira
M H
MH
Hayashida
C Y
CY
Toledo
S P
SP
Abelin
N
N
Levine
M A
MA
Bowers
C Y
CY
Souza
A H
AH
Pereira
R M
RM
Santos
N L
NL
Salvatori
R
R
D000324:Adrenocorticotropic Hormone / Q000097:blood; D006728:Hormones / Q000494:pharmacology; D019382:Human Growth Hormone / Q000172:deficiency* / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood; D009154:Mutation; D009842:Oligopeptides / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood
D006728:Hormones; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013972:Thyrotropin; C091874:growth hormone-releasing peptide-2; C048250:somatotropin releasing hormone receptor; D006854:Hydrocortisone