Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 1/19/2005
Publication Date: 4/2/2005
Citation: Oliver, W.T., Lopez, R., Cummings, K.K., Rosenberger, J., Fiorotto, M.L. 2005. Functional significance of developmental changes in muscle IGFBPs for IGF-I signaling [abstract]. The Federation of American Societies for Experimental Biology Conference. Part II(abstract 579.3):A985. Interpretive Summary: Not Required for an Abstract.
Technical Abstract: We have demonstrated that in skeletal muscle IGFBP 3 abundance decreases in males and increases in females with development, while IGFBP 4 and 5 increase in both genders; how this affects ligand activation of the IGF-I receptor (IGF-1R) is uncertain. We hypothesized that developmental changes in muscle IGFBP abundances would suppress IGF-I-induced activation of the muscle IGF-1R. To test this, we compared the efficacy of activation of the IGF-IR by equimolar exogenous LR3-IGF-I (LR3; with negligible affinity for IGFBPs) and IGF-I. At 5 and 10 wk of age mice were injected iv with LR3 or IGF-I at one of six doses (0.025 to 2.5 mg/kg BW). Five minutes later, the mice were killed, quadriceps were recovered, and muscle IGF-1R abundance and tyrosine phosphorylation were measured by Western analysis. IGF-1R abundance did not differ between 5 and 10 wk of age (P > 0.05). The degree of tyrosine phosphorylation of the IGF-1R was dose dependent and was greater (P < 0.01), on average, for mice injected with LR3 (0.70 +/- 0.01) compared to IGF-I (0.63 +/- 0.02), regardless of gender or age (P > 0.05). Maximal phosphorylation was 0.88 +/- 0.05 (LR3) and 0.76 +/- 0.06 (IGF-I, P < 0.01) at the highest dose, regardless of age (P > 0.05). Thus, local IGFBPs inhibit the ability of exogenous IGF-I to activate the IGF-IR but the magnitude of their change with age and gender are insufficient to alter materially IGF-IR activation.