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-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 ahs 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 micrograms/kg i.v. GHRP-2 and HEX comparing them with that after 1 micrograms/kg i.v. GHRH and 400 micrograms i.v. TRH + 2 micrograms/kg i.v. hCRH. The Gh responses to 2 micrograms/kg i.v. GHRP-2 or HEX, compared with those to 1 microgram/kg GHRH, were also studied in 6 normal elderly subjects (66-73 yr). In young adults 1 microgram/kg i.v. 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 micrograms/kg i.v. GHRP-2 and HEX again elicited a similar GH response, which was higher (p < 0.05) than that after the 1.0 microgram/kg dose. In elderly subjects, the GH 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) responses were similar to those to hCRH. In conclusion, our results demonstrate that, in man, GHRP-2 and HEX have similar, 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.
Arvat
E
E
Department of Internal Medicine, University of Turin, Italy.
di Vito
L
L
Maccagno
B
B
Broglio
F
F
Boghen
M F
MF
Deghenghi
R
R
Camanni
F
F
Ghigo
E
E
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005483:Flushing / Q000139:chemically induced; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D006133:Growth Substances; D009842:Oligopeptides; D010906:Pituitary Hormone-Releasing Hormones; C086184:hexarelin; D019382:Human Growth Hormone; D013973:Thyrotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; C091874:growth hormone-releasing peptide-2; D006854:Hydrocortisone