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
Abstract
Arvat, E., L. Di Vito, B. Maccagno, F. Broglio, M. F. Boghen, R. Deghenghi, F. Camanni and E. Ghigo. 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. Peptides 18(6) 885–891, 1997.—GHRP-2 (d-Ala-d-βNal-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 μg/kg IV GHRP-2 and HEX comparing them with that after 1 μg/kg IV GHRH and 400 μg IV TRH + 2 μg/kg IV hCRH. The GH responses to 2 μg/kg IV GHRP-2 or HEX, compared with those to 1 μg/kg GHRH, were also studied in 6 normal elderly subjects (66–73 yr). In young adults 1 μg/kg IV 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 μg/kg IV GHRP-2 and HEX again elicited a similar GH response, which was higher (p < 0.05) than that after the 1.0 μg/kg dose. In elderly subjects, the GH responses to 2.0 μg/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.
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Section snippets
Peptides and Drugs
Vials containing 100 μg of lyophilized Hexarelin (HEX) (Mwt 887.06) and GHRP-2 (Mwt 817.97) were kindly provided by Europeptides (Argenteuil, France). Vials containing 50 μg lyophilized GHRH-(1–29) (Mwt 5039.7) (GEREF) were purchased from Serono (Milan, Italy). Vials containing 200 μg TRH (Mwt 354.4) (TRH) and vials containing 100 μg hCRH (Mwt 4757.5) (Human CRH) were purchased from Ferring (Kiel, Germany). Hexarelin, GHRP-2, GHRH, TRH and hCRH have been administered as an IV bolus.
Study Design
Six normal
Results
Basal GH, PRL, ACTH and cortisol levels were similar in all tests both in young and in elderly subjects, while basal IGF-I levels in young were higher than in elderly subjects (236.5 ± 28.8 vs. 107.0 ± 8.37 μg/l, p < 0.01).
Discussion
Our present findings show that, in humans, GHRP-2 and Hexarelin have the same, dose- and age-dependent stimulatory effect on somatotrope secretion, releasing more GH than does the maximal effective dose of GHRH. On the other hand, GHRP-2 and Hexarelin have also similar, slight stimulatory effect on PRL, ACTH and cortisol secretion. Notably, the PRL-releasing activity of both GHRP-2 and Hexarelin is lower than that of TRH while their ACTH/cortisol-releasing activity is similar to that of hCRH,
Acknowledgements
The authors wish to thank Dr. L. Gianotti and J. Ramunni for participating in the study and Dr. A. Bertagna, Mrs. A. Barberis and M. Taliano for their skillful technical assistance. This study was supported by grants from CNR (Progetto Finalizzato Invecchiamento 97/3/705), MURST, Europeptides and FSMEM.
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