The local expression and abundance of insulin-like growth factor (IGF) binding proteins in skeletal muscle are regulated by age and gender but not local IGF-I in vivo.
We wished to determine whether sustained IGF-I production in skeletal muscle increases local IGF binding protein (IGFBP) abundance, thereby mitigating the long-term stimulation of muscle growth by IGF-I. Muscle growth of transgenic mice that overexpress IGF-I in muscle (SIS2) and of wild-type (Wt) mice was compared. At 3, 5, 10, and 20 wk of age, hind-limb muscle weights and IGFBP-3, -4, -5, and -6 mRNA and protein abundances were quantified. Additional mice were injected with IGF-I or LR3-IGF-I, and phosphorylation of the type 1 IGF receptor (IGF-1R) was compared. Muscle mass was 20% greater in SIS2 compared with Wt mice by 10 wk of age (P < 0.01), and this difference was maintained to 20 wk. IGFBP mRNA and protein abundances were unaffected by genotype. IGFBP-4 and -5 protein abundances increased with age, whereas for IGFBP-3 and -6, there was a sexual dimorphic response (P < 0.01); after 5 wk of age, IGFBP-3 decreased in males but increased in females, whereas IGFBP-6 decreased in females and remained unchanged in males. These protein expression patterns resulted from differences at both the transcriptional and posttranscriptional levels. LR3-IGF-I stimulated IGF-1R phosphorylation to a greater extent than IGF-I at both 5 and 10 wk of age (P < 0.01), regardless of gender or genotype (P > 0.21). Thus, variations in local IGF-I levels do not appear to regulate muscle IGFBP expression. The age- and gender-specific differences in muscle IGFBP expression are not sufficient to alter the response of the muscle to the IGFs but may impact the IGF-independent effects of these IGFBPs.
Oliver
William T
WT
United States Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Rosenberger
Judy
J
Lopez
Rusmely
R
Gomez
Adam
A
Cummings
Kathleen K
KK
Fiorotto
Marta L
ML
D000375:Aging / Q000378:metabolism*; D000818:Animals; D005260:Female; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000378:metabolism*; D009929:Organ Size; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012727:Sex Characteristics
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1