Bioactivity of growth hormone releasing hormone (1-29) analogues after SC injection in man.

Peptides1989PMID: 2546126

Plain Language Summary

A supposedly superactive GHRH analogue that showed greatly enhanced potency in rats was compared to standard GHRH 1-29 in human volunteers, but both produced equivalent growth hormone responses and had similar blood levels and clearance rates. This species difference suggests that the enhanced activity seen in rats does not translate to humans, possibly due to differences in how the GHRH receptor interacts with modified peptides between species. The finding is important for drug development, as it shows rat data may not predict human efficacy for GHRH analogues.

Abstract

The bioactivity of growth hormone releasing hormone 1-29 [GHRH(1-29)NH2] has been compared with that of an agonist analogue [Ac-D-Tyr1,D-Ala2]-GHRH(1-29)NH2, in normal male volunteers. Using a submaximal dose of 3 micrograms/kg administered subcutaneously, peak growth hormone (GH) response and area under the GH curve were similar for the native and agonist analogue. In addition, no significant differences were found in peak GHRH(1-29) immunoreactivity, area under the GHRH(1-29) curves or plasma disappearance rates of the two peptides. The results suggest that, in keeping with the relative activities of other "superactive" analogues tested so far, the greatly enhanced activity of [Ac-D-Tyr1,D-Ala2]-GHRH(1-29)NH2 observed in the rat is not found in humans. It is possible that this species difference is due to differences in the interaction of GHRH peptides with the rat and the human somatotroph GHRH receptor.

Authors

Aitman, T J; Rafferty, B; Coy, D; Lynch, S S; Clayton, R N