PMID- 8921821
OWN - NLM
STAT- MEDLINE
DCOM- 19961230
LR  - 20190905
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 135
IP  - 4
DP  - 1996 Oct
TI  - Short-term administration of intranasal or oral Hexarelin, a synthetic 
      hexapeptide, does not desensitize the growth hormone responsiveness in human 
      aging.
PG  - 407-12
AB  - The function of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis 
      is reduced in aging, although the secretory capacity of somatotrope cells is 
      preserved. Previous studies have suggested that continuous administration of 
      GH-releasing peptides (GHRPs) results in homologous desensitization to the 
      GH-releasing effect of the peptides. In the present study we have studied whether 
      healthy elderly subjects would remain responsive to short-term, intermittent 
      treatment with Hexarelin (HEX), a GHRP, and whether this treatment would result 
      in an increase in serum IGF-I. In study I, the effect of an 8-day treatment with 
      intranasal administration of 1.25 mg (about 18 micrograms/kg) t.i.d. HEX on the 
      acute GH response to the hexapeptide and on serum IGF-I, IGF binding protein 3 
      (IGFBP-3), prolactin and cortisol levels was studied in seven elderly subjects 
      (four males and three females, aged 67-80 years). In study II, the same 
      parameters were studied before and after a 15-day treatment with oral 
      administration of 20 mg (about 300 micrograms/kg) t.i.d. HEX in seven elderly 
      women (aged 63-80 years). The GH response to the intranasal HEX administration 
      was not significantly higher than that induced by 1 microgram/kg iv GHRH (229.4 
      +/- 35.9 vs 145.8 +/- 26.9 micrograms.l-1.h-1) and was maintained with a trend 
      towards increase after an 8-day treatment with the peptide (342.5 +/- 199.3 
      micrograms.l-1.h-1). On the other hand, HEX treatment did not significantly 
      modify IGF-I (138.7 +/- 11.1 vs 122.4 +/- 14.1 micrograms/l) but increased 
      IGFBP-3 levels (2.4 +/- 0.2 vs 1.6 +/- 0.2 mg/l, p < 0.02). The GH response to 
      the oral HEX administration was also not significantly higher than that to iv 
      GHRH (257.6 +/- 72.0 vs 179.0 +/- 42.8 micrograms.l-1.h-1) and did not change 
      after a 15-day treatment with the peptide (237.8 +/- 42.8 micrograms.l-1.h-1). 
      Both IGF-I and IGFBP-3 levels were slightly but significantly increased by oral 
      HEX treatment (156.0 +/- 10.7 vs 141.6 +/- 13.6 micrograms/l, p < 0.03, 3.4 +/- 
      0.2 vs 3.1 +/- 0.2 mg/l, p < 0.03, respectively). Neither intranasal nor oral HEX 
      treatment modified PRL or cortisol levels and did not induce any side effect. In 
      conclusion, these results indicate that chronic but intermittent treatment with 
      HEX, administered either by intranasal or oral route, does not desensitize the GH 
      response to the peptide. Moreover, after HEX treatment a trend towards increase 
      was shown for IGF-I and IGFBP-3 levels. Thus, our findings strengthen the 
      hypothesis that prolonged treatment with HEX may restore the reduced GH release 
      in aging.
FAU - Ghigo, E
AU  - Ghigo E
AD  - Division of Endocrinology, University of Turin, Italy.
FAU - Arvat, E
AU  - Arvat E
FAU - Gianotti, L
AU  - Gianotti L
FAU - Grottoli, S
AU  - Grottoli S
FAU - Rizzi, G
AU  - Rizzi G
FAU - Ceda, G P
AU  - Ceda GP
FAU - Boghen, M F
AU  - Boghen MF
FAU - Deghenghi, R
AU  - Deghenghi R
FAU - Camanni, F
AU  - Camanni F
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Oligopeptides)
RN  - 09QF37C617 (hexarelin)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Administration, Intranasal
MH  - Administration, Oral
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/*physiology
MH  - Female
MH  - Human Growth Hormone/metabolism/*physiology
MH  - Humans
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Male
MH  - Middle Aged
MH  - Oligopeptides/*administration & dosage/pharmacology
MH  - Time Factors
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
AID - 10.1530/eje.0.1350407 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 1996 Oct;135(4):407-12. doi: 10.1530/eje.0.1350407.