EFFECTS OF GHRP-2 AND HEXARELIN, 2 SYNTHETIC GH-RELEASING PEPTIDES, ON GH, PROLACTIN, ACTH AND CORTISOL-LEVELS IN MAN - COMPARISON WITH THEEFFECTS OF GHRH, TRH AND HCRH

GHRP-2 (D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2) and Hexarelin (HEX) (H is-D-2-methylTrp-Ala-Trp-DPhe-Lys-NH2) are synthetic, non-natural supe r-analogs of GHRP-6 endowed with potent stimulatory effect on GH secre tion and slight stimulatory effect on PRL, ACTH and cortisol levels. T heir GH-releasing activity has never been compared each other and thei r 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, wh ich 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 elderl y subjects, the GH responses to 2.0 mu g/kg IV GHRP-2 and HEX were sim ilar 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 do ses of GHRP-2 or HEX were similar and lower (p < 0.01) than that to TR H. On the other hand, all doses of GHRP-2 and HEX stimulated to the sa me extent both ACTH and cortisol. These responses were similar to thos e to hCRH. In conclusion, our results demonstrate that, in man, GHRP-2 and HEX have similar, dose-and age-dependent stimulatory effect on so matotrope secretion, releasing more GH than GHRH. The activity of both GHRP-2 and HEX is not fully specific, as they induce similar increase s in PRL, ACTH and cortisol levels. The PRL-releasing activity of GHRP s is lower than that of TRH while their ACTH/cortisol-releasing activi ty is similar to that of hCRH. (C) 1997 Elsevier Science Inc.