Growth hormone (GH)-releasing effects of synthetic peptide GH-releasing peptide-2 and GH-releasing hormone (1-29NH 2) in children with GH insufficiency and idiopathic short stature

• Published in: Metabolism, clinical and experimental clinical and experimental, 1995-09, Vol.44 (9), p.1199-1204
• Main Authors: Tuilpakov, Anatoly N., Bulatov, Aleksander A., Peterkova, Valentine A., Elizarova, Galine P., Volevodz, Natalya N., Bowers, Cyril Y.
• Format: Article
• Language: English
• Subjects: Adolescent; Body Height; Child; Drug Therapy, Combination; Female; Growth Hormone - blood; Growth Hormone - deficiency; Humans; Kinetics; Male; Oligopeptides - administration & dosage; Oligopeptides - therapeutic use; Sermorelin - administration & dosage; Sermorelin - therapeutic use
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/0026-0495(95)90016-0

To investigate how growth hormone (GH)-releasing peptide (GHRP) and GH-releasing hormone (GHRH) interact in patients with short stature, we examined the acute effects of GHRH1-29NH 2, GHRP-2, and the combination of GHRH1-29NH 2 and GHRP-2 on GH release in children with GH insufficiency ([GHI] group A) and idiopathic short stature ([ISS] group B). Ten children with GHI (aged 11.8 ± 1.1 years; height, −4.2 ± 0.5 SDS) and five children with ISS (aged 11.1 ± 1.2 years; height, −3.2 ± 0.1 SDS) were studied. Intravenous bolus infusions of GHRH1-29NH 2 (1 μg/kg), GHRP-2 (1 μg/kg), and GHRH plus GHRP-2 (each 1 μg/kg), were administered in a randomized order. Because of the variability of GH responses, results were analyzed by a nonparametric statistical method. Patients in group A showed low GH responses to both GHRH1-29NH 2 and GHRP-2 stimulation: in only three of 10 and one of nine cases, respectively, were the peak GH levels above 5.0 μg/L. GH area under the curve (AUC) 90 minutes after GHRP-2 administration was slightly less than for GHRH1-29NH 2 (179 ± 150 v 214 ± 68 μg/L · min, P = .06). In group B, GH responses to GHRH1-29NH 2 and GHRP-2 were approximately of the same magnitude (1,943 ± 819 v 1,981 ± 887 μg/L · min, P = .9). After a combined challenge with GHRH1-29NH 2 and GHRP-2, five of eight children in group A had peak GH concentrations greater than 5 μg/L. GH AUC of the GHRH1-29NH 2 plus GHRP-2 test in group A (1,136 ± 764 μg/L · min) was significantly greater than GH AUC of the GHRP-2 bolus ( P = .02) but was not different from GH AUC of GHRH1-29NH 2 ( P = .09). A dramatic response to combined GHRH1-29NH 2 and GHRP-2 administration was observed in group B, with peak GH levels above 100 μg/L in four of five children. GH AUC of the GHRH1-29NH 2 and GHRP-2 combined study (7,035 ± 1,513 μg/L · min) was significantly greater than the AUC obtained after administration of GHRH1-29NH 2 (1,943 ± 819 μg/ L · min, P = .015) or GHRP-2 (1,982 ± 887, P = .014) alone. Thus, although intravenous bolus GHRP-2 was shown to release GH in children with various forms of short stature, the response is likely to be dependent on the presence of endogenous or exogenous GHRH.