A Placebo-Controlled Trial of Intranasal Growth Hormone-Releasing Hormone [GHRH(l-44)-NH₂] Administration in Normal Young Adults

Abstract

Growth hormone-releasing hormone, GHRH(l-44), was administered intranasally to 16 healthy young adult male volunteers in a placebo-controlled study using a dose of 1,000 µg dissolved in two different solvent vehicles: water alone and water with the surface tension-lowering agent Tween 80 (0.12%). The growth hormone (GH)-releasing effects of intranasal GHRH as well as that of the vehicle were established and compared to the effects of 80 µg intravenous GHRH. Plasma GH response was assessed by frequent blood sampling over an 180-min period, using both peak response and area under the curve (AUC). The results show that the GH-releasing effects of intranasal GHRH are comparable whichever vehicle is used, and are similar, with the dose of 1,000 µg, to the response obtained following the administration of 80 µg intravenous GHRH. Peak GH responses to GHRH (means ± SEM) were 25.6 ± 4.2 ng/ml (1,000 µg GHRH with water), 32.9 ± 9.1 ng/ml (1,000 µg with water plus Tween 80) and 36.3 ± 7.8 ng/ml (80 µg i.v. administration) (not significant). There was no significant GH response to placebo. Mean peak GH responses occurred after approximately 30 min in all three active treatments (29.2 ± 2.7, 33.9 ± 3.2 and 30.9 ± 3.9 min, respectively). The AUC values (ng·min· ml”1) were not statistically different: 1,914.4 ± 386.7 (water), 2,176.2 ± 599.9 (water plus Tween 80) and 2,419.2 ± 506.9 (i.v.) (not significant). Intranasal GHRH administration was well tolerated in all subjects. Occasional local reactions consisted of a prickly sensation in the nostrils or sneezing irrespective of the vehicle used. Long-term tolerance should be established before considering trial of intranasal GHRH administration in the treatment of GH-deficient children.

A Novel Non-Peptidyl Growth Hormone Secretagogue

“…GRF has been shown to be effective in treating children with GH deficiency because of a hypothalamic disorder [3,4], However, the smallest analogues of GRF having full intrinsic biological activity still require the first 29 amino acids of the N terminus [5], GRF is orally inactive but is effective when given intranasally in addition to intravenous and subcutaneous administrations [6,7], GHRP-6 is a synthetic hexapeptide derived from en kephalin through computer modelling techniques [8,9], It stimulates the release of GH from pituitary cells via a unique mechanism which is different from that of GRF [10][11][12], Our data indicate that protein kinase C appears to play a major role in mediating the effect of GHRP-6 [12]. In addition to its in vitro effect, GHRP-6 also stimu lated GH secretion when given intravenously in a number of species including humans [9.…”

Intranasal administration of growth hormone‐releasing hormone(1–29)‐NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth

“…These findings suggested that GHRH, which in earlier trials did not show any serious side-effects (6,7), could be used as a therapeutic agent in children with hypothalamic GHD. A I-month trial in normal young adults has not shown a decline in plasma levels of GHRH and GH after intranasal administration of GHRH (8). Intranasal administration of GHRH to promote growth could thus be an attractive alternative to daily injections of GH.…”