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

The aim of this study was to evaluate the GH-releasing activity of a synthe tic hexapeptide, GHRP-6, in the Prader-Willi syndrome (PWS). Sixteen PWS pa tients (7 males and 9 females, aged 12.7-38.3 yr), 15 with essential obesit y (OB) (7 males and 8 females, aged 12.9-42.9 yr), and 8 short normal child ren (SN; 3 males and 5 females, aged 10.2-14.3 yr) underwent 2 tests on sep arate occasions, being challenged with GHRP-6(1 mug/kg, iv) or GHRH (1 mug/ kg, iv)+PD (60 or 120 mg for children or adults, po). Moreover, in 11 patie nts with PWS and in the group of SN, the GH response to at least 2 stimulat ion tests had been previously determined. GH was analyzed either as mean pe ak values (GHp, mcg/l), or as the area under the curve (AUC, mcg/l/h) and t he net incremental area under the curve (nAUC, mcg/l/h). In the group of PW S subjects, GH responses to both GHRP-6 (GHp: 11.4 +/-2.0; AUG: 588 +/- 113 ; nAUC: 483 +/- 108) and GHRH+PD (GHp: 7.3 +/-1.8; AUG: 486 +/- 1122; nAUC: 371 +/- 250) were significantly lower than those observed either in OB (GH RP-6: GHp: 25.7 +/-3.2, p <0.003; AUG: 1833 +/- 305, p <0.005; nAUC: 1640 /- 263, p <0.0001. GHRH+PD: GHp: 15.1 +/-2.4 p <0.009; AUG: 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; AUG: 2792 +/- 158, p <0.0001; nAUC: 2705 +/- 165, p <0.0 0005. GHRH+PD: GHp: 27.5 +/-3.7, p <0.0001; AUG: 1873 +/- 251, p <0.0001; n AUC: 1692 +/- 219, p <0.0005). Unlike control groups, in PWS patients GH le vels after GHRP-6 did not differ from those obtained after GHRH+PD. Interes tingly, low IGF-I values were present in all PWS subjects. Furthermore, no patient with PWS showed normal GH response to the previously performed GH s timulation tests. As already reported, GH release after GHRP-6 or GHRH+PD w as significantly lower in OB than in SN subjects. In conclusion, our data i ndicate that: 1) GH response to GHRP-6 is clearly impaired in PWS; 2) the b lunted GH responses to the provocative stimuli in PWS are not an artifact o f obesity; 3) short stature in PWS is caused by a complex dysfunction of th e hypothalamo-pituitary structures.