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A 29 amino acid analog of growth hormone releasing hormone (GH-RH)-40 was given intravenously, subcutaneously, and intranasally to normal men to determine its effectiveness in stimulating growth hormone (GH) release. The GH-RH analog, [Nle27]GH-RH(l-29)-NH2, is an amidated 29 amino acid peptide that has one amino acid substitution at position 27. This peptide stimulates GH secretion when given by the intravenous, subcutaneous, and intranasal routes without adverse effect. The degree of GH stimulation was variable among subjects and the greatest amount of stimulation occurred with the highest doses. GH stimulation occurred in a dose-responsive manner after all three routes of administration. A tenfold higher subcutaneous dose was required to stimulate a comparable amount of GH secretion as compared with intravenous administration, and a thirtyfold higher intranasal than intravenous dose was required to stimulate approximately one fifth the amount of GH release. For comparison, one dose of GH-RH-40, 1 µg/kg, was administered intravenously. GH secretion after 1 µg/kg GH-RH-40 and 1 µg/kg Nle27 GH-RH was comparable between the two groups of subjects. Stimulation of GH secretion by Nle27 GH-RH occurred within 5 minutes of intravenous and within 10 minutes of subcutaneous and intranasal administration; peak GH levels were observed within 30 minutes. GH levels declined and returned to near baseline levels 2 hours after administration of the analog. Since GH-RH-40 has been demonstrated to be effective in stimulating GH release and promoting acceleration of linear growth in GH-deficient children, it is likely that a shorter peptide with full biologic activity such as Nle27 GH-RH may also be effective in the treatment of some children with GH deficiency. Clinical Pharmacology and Therapeutics (1986) 40, 627–633; doi:10.1038/clpt.1986.237

Hypothalamic growth hormone-releasing factors (GRFs) have been purified recently from human pancreatic (hp) tumours1,2 and from rat hypothalamus (rh)3. GRF peptides have strong homology with peptides of the glucagon, vasoactive intestinal polypeptide and PHI-27 family. Aside from their potent actions on release of somatotropin, no other biological actions of GRFs have been reported. GRF has been localized in neurones bordering the ventromedial hypothalamic nucleus (refs 4, 5; L. Swanson and P. Sawchenko, manuscript in preparation), a region associated frequently with experimental analysis of feeding behaviour6. We now report that intracerebroventricularly (i.c.v.)-administered rhGRF and hpGRF(1–40) in doses of 0.2, 2.0 and 20.0 pmol, produced an increase in food intake in hungry rats. This effect seemed to be specific to GRF as i.c.v. injections of a structurally related but physiologically inactive peptide7 in the same doses had no effect on feeding. In addition, peripheral injections of rhGRF or growth hormone had no effect on food intake, suggesting that the present effects may be mediated centrally. Injections (i.c.v.) of rhGRF (0.2, 2.0 and 20.0 pmol) had no effect on general activity, suggesting that GRF does not produce nonspecific arousal.

GROWTH HORMONE (GH) RELEASE IN CHILDREN WITH SHORT STATURE: STIMULATION BY HUMAN PANCREATIC TUMOR GROWH HORMONE RELEASING FACTOR-40 (hpGRF-40)