Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH

GHRP-2 (D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2) and Hexarelin (HEX) (His-D-2-methylTrp-Ala-Trp-DPhe-Lys-NH2) are synthetic, non-natural super-analogs of GHRP-6 endowed with potent stimulatory effect on GH secretion and slight stimulatory effect on PRL, ACTH and cortisol levels. Their GH-releasing activity has never been compared each other and their effects on PRL, ACTH and cortisol have never been compared with that of other stimuli. To clarify these points, in 6 normal young adults (22-27 yr) we studied the GH, PRL, ACTH and cortisol responses to 1 and 2 mu g/kg IV GHRP-2 and HEX comparing them with that after 1 mu g/kg IV GHRH and 400 mu g TV TRH + 2 mu g/kg IV hCRH. The GH responses to 2 mu g/kg IV GHRP-2 or HEX, compared with those to 1 mu g/kg GHRH, were also studied in 6 normal elderly subjects (66-73 yr). In young adults 1 mu g/kg TV GHRP-2 and HEX induced a similar, strong GH response, which was higher (p < 0.05) than that to GHRH. The administration of 2.0 mu g/kg IV GHRP-2 and HEX again elicited a similar GH response, which was higher (p < 0.05) than that after the 1.0 mu g/kg dose. In elderly subjects, the GH responses to 2.0 mu g/kg IV GHRP-2 and HEX were similar and higher than that to GHRH (p < 0.05) but lower (p < 0.01) than those in young subjects. In young adults, the PRL responses to all doses of GHRP-2 or HEX were similar and lower (p < 0.01) than that to TRH. On the other hand, all doses of GHRP-2 and HEX stimulated to the same extent both ACTH and cortisol. These responses were similar to those to hCRH. In conclusion, our results demonstrate that, in man, GHRP-2 and HEX have similar, dose-and age-dependent stimulatory effect on somatotrope secretion, releasing more GH than GHRH. The activity of both GHRP-2 and HEX is not fully specific, as they induce similar increases in PRL, ACTH and cortisol levels. The PRL-releasing activity of GHRPs is lower than that of TRH while their ACTH/cortisol-releasing activity is similar to that of hCRH. (C) 1997 Elsevier Science Inc.