Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin).
OBJECTIVE
Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide.


METHODS
Ten children with familial short stature (FSS) aged 5.5-15.5 years and two known GH deficient patients aged 24 and 28 years without GH treatment.


METHODS
All 12 subjects were submitted to i.v. (1 microgram/kg) and i.n. (20 micrograms/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA).


RESULTS
Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (+/- SD) being 72.2 +/- 35.5 mU/l for the i.n. test and 79.6 +/- 53.0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15-30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response in either test. Plasma TSH decreased in the FSS children from a mean (+/- SD) of 1.0 +/- 0.26 to 0.64 +/- 0.2 mU/l (P < 0.005) during the i.n. test and from 1.0 +/- 0.3 to 0.7 +/- 0.3 mU/l (P < 0.05) during the i.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1.06 +/- 0.38 mU/l to 0.86 +/- 0.17 during the i.v. test and from 1.60 +/- 0.01 to 1.11 +/- 0.06 mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests.


CONCLUSIONS
The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intranasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.
Laron
Z
Z
Endocrinology and Diabetes Research Unit, Children's Medical Center of Israel, Petah Tikva.
Frenkel
J
J
Gil-Ad
I
I
Klinger
B
B
Lubin
E
E
Wuthrich
P
P
Boutignon
F
F
Lengerts
V
V
Deghenghi
R
R
D000281:Administration, Intranasal; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D013006:Growth Hormone / Q000097:blood* / Q000172:deficiency; D006133:Growth Substances / Q000008:administration & dosage*; D006728:Hormones / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D013972:Thyrotropin / Q000097:blood
D006133:Growth Substances; D006728:Hormones; D009842:Oligopeptides; C086184:hexarelin; D013972:Thyrotropin; D013006:Growth Hormone