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Impairment of GH responsiveness to GH-releasing hexapeptide (GHRP-6) in Prader-Willi syndrome.

Abstract
The aim of this study was to evaluate the GH-releasing activity of a synthetic hexapeptide, GHRP-6, in the Prader-Willi syndrome (PWS). Sixteen PWS patients (7 males and 9 females, aged 12.7-38.3 yr), 15 with essential obesity (OB) (7 males and 8 females, aged 12.9-42.9 yr), and 8 short normal children (SN; 3 males and 5 females, aged 10.2-14.3 yr) underwent 2 tests on separate occasions, being challenged with GHRP-6 (1 microg/kg, iv) or GHRH (1 microg/kg, iv)+PD (60 or 120 mg for children or adults, po). Moreover, in 11 patients with PWS and in the group of SN, the GH response to at least 2 stimulation tests had been previously determined. GH was analyzed either as mean peak values (GHp, mcg/l), or as the area under the curve (AUC, mcg/l/h) and the net incremental area under the curve (nAUC, mcg/l/h). In the group of PWS subjects, GH responses to both GHRP-6 (GHp: 11.4+/-2.0; AUC: 588+/-113; nAUC: 483+/-108) and GHRH+PD (GHp: 7.3+/-1.8; AUC: 486+/-122; nAUC: 371+/-250) were significantly lower than those observed either in OB (GHRP-6: GHp: 25.7+/-3.2, p<0.003; AUC: 1833+/-305, p<0.005; nAUC: 1640+/-263, p<0.0001. GHRH+PD: GHp: 15.1+/-2.4, p<0.009; AUC: 1249+/-248, p<0.003; nAUC: 918+/-230, p<0.006) or in SN patients (GHRP-6: GHp: 39.1+/-3.1, p<0.0001; AUC: 2792+/-158, p<0.0001; nAUC: 2705+/-165, p<0.00005. GHRH+PD: GHp: 27.5+/-3.7, p<0.0001; AUC: 1873+/-251, p<0.0001; nAUC: 1692+/-219, p<0.0005). Unlike control groups, in PWS patients GH levels after GHRP-6 did not differ from those obtained after GHRH+PD. Interestingly, low IGF-I values were present in all PWS subjects. Furthermore, no patient with PWS showed normal GH response to the previously performed GH stimulation tests. As already reported, GH release after GHRP-6 or GHRH+PD was significantly lower in OB than in SN subjects. In conclusion, our data indicate that: 1) GH response to GHRP-6 is clearly impaired in PWS; 2) the blunted GH responses to the provocative stimuli in PWS are not an artifact of obesity; 3) short stature in PWS is caused by a complex dysfunction of the hypothalamo-pituitary structures.
AuthorsG Grugni, G Guzzaloni, F Morabito
JournalJournal of endocrinological investigation (J Endocrinol Invest) Vol. 24 Issue 5 Pg. 340-8 (May 2001) ISSN: 0391-4097 [Print] Italy
PMID11407654 (Publication Type: Journal Article)
Chemical References
  • Oligopeptides
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • growth hormone releasing hexapeptide
  • Growth Hormone-Releasing Hormone
  • Pyridostigmine Bromide
Topics
  • Adolescent
  • Adult
  • Body Mass Index
  • Child
  • Female
  • Growth Hormone-Releasing Hormone
  • Human Growth Hormone (blood)
  • Humans
  • Insulin-Like Growth Factor I (analysis)
  • Kinetics
  • Male
  • Obesity (complications)
  • Oligopeptides
  • Prader-Willi Syndrome (blood, complications)
  • Pyridostigmine Bromide

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