Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats.
Ipamorelin is a new and potent synthetic pentapeptide which has distinct and specific growth hormone (GH)-releasing properties. With the objective of investigating the effects on longitudinal bone growth rate (LGR), body weight (BW), and GH release, ipamorelin in different doses (0, 18, 90 and 450 microg/day) was injected s.c. three times daily for 15 days to adult female rats. After intravital tetracycline labelling on days 0, 6, and 13, LGR was determined by measuring the distance between the respective fluorescent bands in the proximal tibia metaphysis. Ipamorelin dose-dependently increased LGR from 42 microm/day in the vehicle group to 44, 50, and 52 microm/day in the treatment groups (P<0.0001). There was also a pronounced and dose-dependent effect on BW gain. The treatment did not affect total IGF-I levels, IGFBPs, or serum markers of bone formation and resorption. The number of tartrate-resistant acid phosphatase-positive multinuclear cells in the metaphysis of the tibia did not change significantly with treatment. The responsiveness of the pituitary to a provocative i.v. dose of ipamorelin or GHRH showed that the plasma GH response was marginally reduced (P<0.03) after ipamorelin, but unchanged after GHRH. The pituitary GH content was unchanged by ipamorelin treatment. Whether ipamorelin or other GH secretagogues may have a place in the treatment of children with growth retardation requires demonstration in future clinical studies.
Johansen
P B
PB
Department of Pharmacological Research, Novo Nordisk A/S, Bagsvaerd, DK-2880, Denmark. pjoh@novo.dk
Nowak
J
J
Skjaerbaek
C
C
Flyvbjerg
A
A
Andreassen
T T
TT
Wilken
M
M
Orskov
H
H
D000818:Animals; D001835:Body Weight; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006728:Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D006728:Hormones; D009842:Oligopeptides; C114611:ipamorelin