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Growth Hormone-Releasing Peptide-2 Stimulates GH Secretion in GH-Deficient Patients with Mutated GH-Releasing Hormone Receptor¹

Endocrine-Genetics Unit/LIM 25, Department of Medicine, University of Sao Paulo School of Medicine (R.G.G., C.Y.H., N.A., S.P.A.T.), 01246–903 Sao Paulo, Brazil; Division of Endocrinology, Federal University of Sergipe (M.H.A.-O., A.H.O.S., R.M.C.P., N.L.S.), 49060-100 Aracajo Sergipe, Brazil; Division of Endocrinology, Departments of Medicine (M.A.L., R.S.) and Pediatrics (M.A.L.), and the Ilyssa Center for Molecular Endocrinology (M.A.L., R.S.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Department of Medicine, Division of Endocrinology, Tulane University, School of Medicine, Endocrine Section (C.Y.B.), New Orleans, Louisiana 70112

Address all correspondence and requests for reprints to: Dr. Rogério G. Gondo, Endocrine-Genetics Unit/LIM 25, Sao Paulo University School of Medicine, Avenue Dr. Arnaldo, 455/5th Floor, 01246–903 Sao Paulo, Brazil. E-mail: gondo_rog{at}hotmail.com

Abstract

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 µg/L (range, 0.04–2.12 µg/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 µg/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 µg/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 µIU/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.

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