Intranasal administration of His-D-Trp-Ala-Trp-D-Phe-LysNH2 (growth hormone releasing peptide) increased plasma growth hormone and insulin-like growth factor-I levels in normal men.
The effects of intranasal and iv administration of His-D-Trp-Ala-Trp-D-Phe-LysNH2 (GHRP) on plasma GH, PRL, LH, FSH, TSH, cortisol, insulin, IGF-I as well as GHRH-like immunoreactivity (LI) levels were examined in 6 healthy male subjects. An iv bolus injection of GHRP(1 micrograms/kg BW) caused a remarkable increase in plasma GH levels with a mean (+/- SE) peak of 54.9 +/- 4.2-micrograms/L. In addition an intranasal administration of GHRP resulted in a significant, dose-related increase in plasma GH with peaks of 39.6 +/- 15.3 micrograms/L at a dose of 30 micrograms/kg BW, 14.1 +/- 5.0 micrograms/L at 15 micrograms/kg BW and 7.5 +/- 5.7 micrograms/L at 5 microgram/kg BW. Plasma PRL and cortisol levels were slightly but significantly increased after iv administration of GHRP, whereas GHRP totally failed to affect plasma TSH, LH, FSH, insulin, blood sugar and GHRH-LI levels. Seven consecutive, intranasal administrations of 15 micrograms/kg BW GHRP every 8h were well tolerated in all subjects examined. During this treatment, GH responsiveness to GHRP was not attenuated by desensitization and plasma IGF-I was increased from 94.5 +/- 5.8 micrograms/L before GHRP to 125.8 +/- 6.0 micrograms/L after repeated GHRP administration. These findings indicate that intranasal administration of GHRP stimulates GH secretion and consequently enhances IGF-I production in normal subjects. If GHRP is demonstrated to be beneficial in the treatment of some patients with GH deficiency, the intranasal route of administration may be more useful than the painful injection because a prolonged period is required for the treatment.
Division of Metabolism and Nutrition, International Center for Exchanging Medical Research, Kobe, Japan.
S
S
Hayashi
Y
Y
Okimura
H
H
Yagi
T
T
Uchiyama
Y
Y
Takeshima
S
S
Shakutsui
S
S
Oohashi
C Y
CY
Bowers
K
K
Chihara
D000281:Administration, Intranasal; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000097:blood*; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013997:Time Factors
D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D006854:Hydrocortisone