No abstract

Hexarelin (Hex) is a new synthetic hexapeptide with potent growth hormone (GH)-releasing activity in both animals and men. We evaluated the GH response to a maximal dose of Hex (2 micrograms/kg iv) and GH-releasing hormone (GHRH) (1-29, 1 microgram/kg iv) in 45 short normal children (24 males and 21 females, age 5.9-14 yr, 24 prepubertal and 21 in Tanner stage 2 or 3 of pubertal maturation), in 10 prepubertal obese children (7 males and 3 females, age 7.5-12 yr), and in 5 subjects with organic hypopituitarism (4 males and 1 female, age 8.4-21 yr). In 5 male subjects with constitutional growth delay (age 12.0-13.7 yr), the GH response to Hex was reevaluated 1 week after priming with testosterone enanthate (100 mg im). In all short normal children Hex caused a prompt and clear-cut increase of serum GH concentrations, with peaks occurring between 15-30 min from injection. The GH response to Hex was significantly higher than that observed after GHRH and was not different between males and females or between prepubertal and pubertal subjects. Priming with testosterone resulted in an increased GH response to Hex in all 5 subjects studied. No GH increase was observed in the hypopituitary subjects after either GHRH or Hex administration. In the obese children the GH responses to GHRH and to Hex were significantly lower than in the prepubertal children. Also, in the obese, the GH response to Hex was significantly higher than that observed after GHRH. In all short normal and obese children, but not in the hypopituitary subjects, Hex administration caused a slight but significant increase from baseline of both cortisol and PRL concentrations that returned to the baseline values within 2 h. None of the subjects experienced adverse side effects after Hex administration. This study shows that, in short normal and obese children, Hex is a potent GH-releasing stimulus with potential clinical utility.

Administration of exogenous human growth hormone (GH) blunts the GH response to physiological as well as pharmacological stimuli, including GH-releasing hormone (GHRH). Hexarelin (Hex) is a new synthetic GH-releasing peptide (GHRP) similar to GHRP-6 with potent GH-releasing activity in animals and men. To determine whether the short-term administration of GH inhibits the Hex-induced GH release, we measured the GH response to Hex (2 micrograms/kg iv) in five normal adult males (age 26-32 yr) three h after an iv bolus of rhGH (2 IU) or saline. Mean incremental change of serum GH from value at time 0 was 47.5 +/- 5.5 and 41.5 +/- 4.1 micrograms/l after saline + Hex and GH + Hex, respectively. Mean incremental area under the curve over baseline was 3216 +/- 586 and 3735 +/- 506 micrograms.min.1 after saline + Hex and GH + Hex, respectively. One of the proposed mechanism of action of GHRPs is to serve as functional somatostatin (SRIH) antagonists, and it is known that GH feeds backs on the hypothalamus to stimulate SRIH release. Therefore, we speculate that antagonisms of SRIH function by Hex prevented the inhibitory effect of exogenous GH, thus lending further support to the hypotheses that SRIH is involved in the feedback regulation of GH secretion, and that GHRPs action involves inhibition of SRIH function.