Massoud, Ahmed Faris; (1997) Growth hormone releasing peptides: Physiological studies in man. Doctoral thesis (M.D), UCL (University College London).

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Abstract

This work describes physiological studies of the growth hormone releasing peptide (GHRP) hexarelin. Four groups of studies were conducted on young, healthy, adult male volunteers, as follows; 1. Studies which demonstrated that hexarelin is a potent growth hormone (GH) secretagogue, capable of inducing GH release after two successive administrations. GHRP acts synergistically with growth hormone releasing hormone (GHRH) to induce massive GH release. However, this synergistic action is lost on repeated administration. 2. Studies which showed that GH itself attenuates the GH response to GHRP. 3. Studies which showed that the GH-releasing activity of GHRP, alone or in combination with GHRH, is attenuated but not abolished by increasing somatostatin (SS) tone. The large GH release induced by GHRP plus GHRH despite the presence of high SS tone suggests that combined therapy may be utilised to produce GH release in conditions where SS tone is unknown. 4. Studies which established GH dose-response curves for hexarelin. This group of studies also showed that hexarelin is non-specific for GH release, inducing prolactin (PRL) and cortisol release in a dose-related manner. These studies showed that at low doses of hexarelin it is possible to induce adequate GH release with minimum concomitant rise in PRL and cortisol. Moreover, combined GHRH plus low dose hexarelin is synergistic for GH release with no additive effect on PRL and cortisol release. The actions of GHRPs and their interaction with the two main endogenous regulators of GH secretion, namely, GHRH and SS, strongly suggests that an endogenous GHRP ligand exists and plays an important role in the regulation of GH release. The specific GH release induced by low doses of GHRP, alone or in combination with GHRH, together with the oral activity of these peptides, holds a great promise for future therapeutic use.

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