Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children.
A clinical, prospective experiment was carried out to determine whether long-term intranasal administration of the growth hormone-releasing peptide hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe -Lys-NH2) affects pituitary growth hormone secretion. Hexarelin (60 micrograms/kg t.i.d.) was administered to seven prepubertal constitutionally short children (mean age +/- SD = 7.6 +/- 2.4 years). Serum human growth hormone (hGH) response to an intranasal (20 micrograms/kg) and i.v. (1 mircogram/kg) bolus of hexarelin before, during and after 6-10 months of treatment was measured. The mean ( +/- SD) peak rise of hGH to the intranasal bolus before treatment was 70.6 +/- 28.2 mU/l. After 7 days of hexarelin treatment, mean peak values dropped to 34.1 +/- 15.7 mU/l (p < 0.002) and thereafter remained constant for 6 months of treatment at 37.5 +/- 10.3 mU/l (p < 0.03). The pretreatment peak to th i.v. hexarelin bolus was 84.8 +/- 52.5 mU/l, and at the end of the treatment period it was 19.8 +/- 10.9 mU/l (p < 0.05). Three months after stopping treatment the mean ( +/- SD) hGH response rose to 42.1 +/- 4.7 mU/l (p < 0.005). Growth velocity increased from 5.3 +/- 0.9 cm/year (before treatment) to 7.4 +/- 1.6 cm/year at 6-10 months of treatment (p < 0.005). In conclusion, teh partial suppression of pituitary hGH responsiveness to long-term intranasal hexarelin treatment, probably due to desensitization, does not affect the observed increase in growth velocity.
Klinger
B
B
Pediatric Endocrinology and Diabetes Research Unit, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Silbergeld
A
A
Deghenghi
R
R
Frenkel
J
J
Laron
Z
Z
D000281:Administration, Intranasal; D001827:Body Height / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004361:Drug Tolerance; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000473:pathology*; D013006:Growth Hormone / Q000097:blood; D006133:Growth Substances / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors
D006133:Growth Substances; D009842:Oligopeptides; C086184:hexarelin; D013006:Growth Hormone