The insulin-like growth factor (IGF) system in the mammary gland: role of IGFBP-3 binding protein.

Author(s):  
C. R. Baumrucker
2000 ◽  
Vol 165 (3) ◽  
pp. 545-556 ◽  
Author(s):  
EJ Whellams ◽  
LA Maile ◽  
JK Fernihough ◽  
ME Billingham ◽  
JM Holly

Increased concentrations of insulin-like growth factor (IGF) system components have previously been observed in rheumatoid arthritis (RA) and osteoarthritis (OA); however, disruption of the IGF axis and the implications for the disease process remain largely unaddressed. This study was undertaken to characterise the IGF binding protein (IGFBP)-3 proteolysis and complex formation systems in synovial fluid and to investigate changes in these systems in arthritic disease, and their impact on the availability of IGF. Western blotting or autoradiography of SDS gels was used to visualise IGFBP-3 or its proteolysis. IGF-I and IGFBP-3 concentrations were determined by radioimmunoassays and acid-labile subunit (ALS) was measured by ELISA. A shift in distribution of IGFBP-3 and IGF-I in RA and OA synovial fluids (RASynF, OASynF) and an associated increase in ALS suggested the presence of 150 kDa ternary complexes. IGFBP-3 proteolysis was decreased in RASynF and OASynF, but was apparent in size-fractionated fluid and resembled serum activity. The presence of serum-like inhibitors of IGFBP-3 proteolysis in RASynF was also demonstrated by the ability of this fluid, and 150 kDa fractions from its size fractionation, to inhibit IGFBP-3 proteolysis in the other synovial fluid. A marked disruption in the IGF system was observed, as considerably more IGF-I was retained in ternary complexes. We also classified the IGFBP-3 proteolysis system in synovial fluid and found it to be disturbed in RASynF and OASynF. These changes may be caused by an increased flux of circulatory proteins into synovial fluid, resulting from an inflammation-induced increase in vascular permeability. The net result in RA and OA would be a decrease in IGF availability in arthritic joints, and therefore loss of a potential anabolic stimulus. This disruption to the IGF axis would influence disease progression in RA and OA.


2003 ◽  
Vol 195 (1) ◽  
pp. 70-79 ◽  
Author(s):  
Emily J. Foulstone ◽  
Paul B. Savage ◽  
Anna L. Crown ◽  
Jeff M.P. Holly ◽  
Claire E.H. Stewart

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Ayfer Altas ◽  
Fatih Kuzu ◽  
Dilek Arpaci ◽  
Mustafa Unal ◽  
Murat Can ◽  
...  

Aim.Insulin-like growth factor-1 (IGF-1) is a potent mitogen for many cells. IGF-1 plays a role in the pathogenesis of various tumors with its mutagenic and antiapoptotic properties. The aim of this study was to determine both the serum and intranodular levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with nodular thyroid diseases.Materials and Methods.In this study, 80 subjects who performed fine-needle aspiration biopsy (FNAB) were required in order to investigate the effects of serum and intranodular IGF-1 and IGFBP-3 in the pathogenesis of nodules. After performing FNAB, IGF-1 and IGFBP-3 levels were determined in blood and aspiration samples.Results.The serum levels of IGF-1 (232.8 ± 12.9 ng/ml) and IGFBP-3 (4.8 μg/ml) were found significantly higher than that of the intranodular IGF-1 (39.1 ng/ml) and intranodular IGFBP-3 levels (0.173 μg/ml) (p<0.01). Intranodular levels of IGF-1 and IGFBP-3 were higher in subjects with multinodular thyroid gland than those of subjects with solitary nodules (p=0.043). A positive correlation between the nodule size and the serum IGFBP-3 levels was detected (p=0.042,r=0.23).Conclusion.This study demonstrated the possible role of both IGF-1 and IGFBP-3 in the growth and the formation of multinodularity of thyroid nodules.


2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  

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