Anabolic effects of insulin-like growth factor-I (IGF-I) and an IGF-I variant in normal female rats.
Administration of IGF-I over a 14-day period to growing female rats via s.c. implanted osmotic pumps led to an increased body weight gain, an improved N retention and a greater food conversion efficiency. The effects were dose-dependent, with the highest daily dose tested, 278 micrograms/day, producing 18-26% increases in these measurements. LR3IGF-I, a variant of human IGF-I that contains an amino terminal extension peptide as well as glutamate-3 replaced by arginine and exhibits very weak binding to IGF-binding proteins, was substantially more potent than the natural growth factor, in the 44 micrograms/day of this peptide produced similar effects to the high IGF-I dose. Organ weight and carcass composition measurements showed that the two IGF peptides generally maintained body proportions at those existing when the experiment began. Muscle protein synthesis and myofibrillar protein breakdown were both slightly increased by IGF treatment, so that the observed improvement in N retention could not be explained through protein accretion rates calculated from these measures. Infusion of human GH at a dose of 213 micrograms/day did not stimulate body growth. This investigation establishes that IGF peptides stimulate the growth of normal growing animals, with IGF-I variants that bind less well to IGF-binding proteins being more active than IGF-I.
Tomas
F M
FM
Cooperative Research Centre for Tissue Growth and Repair, Child Health Research Institute, Adelaide, South Australia.
Knowles
S E
SE
Chandler
C S
CS
Francis
G L
GL
Owens
P C
PC
Ballard
F J
FJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009124:Muscle Proteins / Q000096:biosynthesis; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009124:Muscle Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D009584:Nitrogen