Journal of Clinical Endocrinology & Metabolism, Vol 80, 2987-2992, Copyright © 1995 by Endocrine Society

ARTICLES

Diagnostic studies with intravenous and intranasal growth hormone- releasing peptide-2 in children of short stature

C Pihoker, R Middleton, GA Reynolds, CY Bowers and TM Badger
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, USA.

GH secretion is primarily regulated by the hypothalamic-releasing hormones GHRH and somatostatin. Additionally, several neurotransmitters act at the hypothalamus and pituitary to modulate GH release. The agents commonly used in clinical practice to diagnose GH deficiency, such as arginine, insulin and L-dopa, act through the neural GH network. Many children with a poor GH response to conventional agents have a significant serum GH response to iv GHRH. GH-releasing peptides (GHRPs) are synthetic peptides that like GHRH act directly on pituitary somatotrophs to stimulate GH release. GHRP-2, an investigational drug, is one of the most potent members of the GHRP family. It has been shown to be effective in adults via the oral and intranasal as well as the iv route of administration. In this study, GH responses to GHRP-2 were compared with GH responses to other provocative agents in children of short stature. GHRP-2 was administered iv or intranasally to children with short stature. In the same subjects, GHRP-2 was administered iv in combination with GHRH. Twenty-four children undergoing evaluation for GH deficiency received at least one conventional agent (arginine, L- dopa/exercise, insulin) in addition to iv GHRH and GHRP-2. The GH responses to GHRH or GHRP-2 were similar in each child, and both were equally reliable predictors of pituitary reserve. The conventional agents used in GH testing were less likely to predict the capacity of the pituitary to release GH than were either GHRH or GHRP-2. There was no correlation between maximal GH response to standard tests with GH responses to GHRH or GHRP-2. A subset of the group of 21 children who had a robust response to iv GHRP-2 were later administered GHRH+GHRP-2 simultaneously. The GH response to GHRH+GHRP-2 was synergistic in this group of 12 children, similar to previously reported observations in adults of normal stature. Fifteen of the 21 children who had a robust response to the iv GH-releasing factors also received intranasal GHRP- 2. All 15 of these children had a significant GH response to intranasal GHRP-2 over a dose range of 5-20 micrograms/kg per dose. The mean peak GH response to 15 micrograms/kg was 31.3 micrograms/L. The intranasal preparation was well tolerated.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin Endocr. Rev., June 1, 2004; 25(3): 426 - 457. [Abstract] [Full Text] [PDF]

				L. Wideman, J. Y. Weltman, J. T. Patrie, C. Y. Bowers, N. Shah, S. Story, A. Weltman, and J. D. Veldhuis Synergy of L-arginine and growth hormone (GH)-releasing peptide-2 on GH release: influence of gender Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1455 - R1466. [Abstract] [Full Text] [PDF]

				L. Wideman, J. Y. Weltman, J. T. Patrie, C. Y. Bowers, N. Shah, S. Story, J. D. Veldhuis, and A. Weltman Synergy of L-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1467 - R1477. [Abstract] [Full Text] [PDF]

				C. Pihoker, G. L. Kearns, D. French, and C. Y. Bowers Pharmacokinetics and Pharmacodynamics of Growth Hormone-Releasing Peptide-2: A Phase I Study in Children J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1168 - 1172. [Abstract] [Full Text]

				I. Shimon, X. Yan, and S. Melmed Human Fetal Pituitary Expresses Functional Growth Hormone-Releasing Peptide Receptors J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 174 - 178. [Abstract] [Full Text]