Growth hormone-releasing peptide (GHRP)-2 is a synthetic six amino acid peptide that is a potent GH secretagogue. Although it shares no structural homology with GH-releasing hormone, in clinical studies its actions on the pituitary release of GH are similar. It is effective when administered orally and intranasally. For children with GH deficiency, such noninvasive treatments are most desirable and in need of development. Fifteen children with short stature participated in this study. All of the children had a height < 2 S.D. below mean for age, poor height velocity, delayed bone age, and low serum concentrations of IGF-1. These children had been tested with standard GH secretagogues, e.g. arginine, insulin, and L-dopa. Fifty percent of the children were GH deficient, the remainder had idiopathic short stature. The children received testing with GHRH and GHRP-2 as an acute i.v. bolus of 1 microgram/kg; all children in this study demonstrated a GH response > 20 micrograms/l. Each child in this study also demonstrated a GH response > 10 micrograms/l in response to intranasal GHRP-2, in the dose range of 5-20 micrograms/kg. The children were administered intranasal GHRP-2, 5-15 micrograms/kg, twice a day for 3 months, then three times a day. Fifteen children participated in the study for 6 months; six of the children have participated for 18-24 months. Height velocity, serum IGF-1, IGF-binding protein 3 (IGFBP-3) and GH-binding protein (GHBP) concentrations, and GH responses to GHRP-2 by i.v. bolus and intranasal spray were examined during treatment. Height velocity increased from 3.7 +/- 0.2 cm/year to 6.1 +/- 0.3 cm/year at 6 months, 6.0 +/- 0.4 cm/year at 18-24 months. There were no significant changes in IGF-1 or IGF-PB3 concentrations, or in acute GH responses to i.v. or intranasal GHRP-2. GHBP concentrations rose significantly, from 439 +/- 63 pmol/l to 688 +/- 48 pmol/l. In this study, intranasal GHRP-2 administration was well tolerated, and produced a modest but significant increase in growth velocity.

Selective neurotoxins have been of value in providing a means for specifically interfering with the actions of endogenous neurotransmitter candidates. Others have shown cysteamine (CSH) to deplete the gastrointestinal tract and hypothalamus of rats of immunoreactive somatostatin, suggesting a toxic action of that compound directed against somatostatin-containing cells. The present study further defines the actions of cysteamine on somatostatin in the central nervous system. (CNS). Cysteamine hydrochloride administered subcutaneously results in a depletion of somatostatin-like immunoreactivity (SLI) in the retina, brain, and cervical spinal cord of rats. The effect is demonstrable at doses of 30 mg/kg of body weight and above, occurs within 2 to 4 hr of a single injection of the drug, and is largely reversible within 1 week. The mean depletion of SLI observed within the CNS varies from 38% in cerebral cortex to 65% in cervical spinal cord 24 hr following administration of CSH, 300 mg/kg of body weight, s.c. By gel permeation chromatography, all molecular weight forms of SLI are affected, with the largest reductions in those forms that co-chromatograph with synthetic somatostatin-14 and somatostatin-28. These results indicate that CSH has a generalized, rapid, and largely reversible effect in depleting SLI from the rat CNS.