Insulin-like growth factors synthesis

Huang, J.S., Mukherjee, J.J., Chung, T., Crilly, K.S. and Kiss, Z. (1999) Extracellular calcium stimulates DNA synthesis in synergism with zinc, insulin and insulin-like growth factor I in fibroblasts. European Journal of Biochemistry 266, 943-951. 

Horney, M.J. et al. (2001) Synthesis and characterization of insulin-like growth factor (IGF)-l photoprobes selective for the IgG-binding proteins (IGFBPs) photoaffinity labeling of the IGF-binding domain on IGFBP-2./. Biol. Chem. 276(4), 2880-2889. 

GH primarily displays an anabolic activity. It partially stimulates the growth of bone, muscle and cartilage cells directly. Binding of GH to its hepatic receptor results in the synthesis and release of insulin-like growth factor (IGF-1), which mediates most of GH s growth-promoting activity on, for example, bone and skeletal muscle (Chapter 7). The major effeets mediated by hGH are summarized in Table 8.6. 

Chakravorty, A. Joslyn, M.L Davis, J.S. Characterization of insulin and insulin-like growth factor-I actions in the bovine luteal cell Regulation of receptor tyrosine kinase activity, phosphatidylinositol 3-kinase, and deoxyribonucleic acid synthesis. Endocrinology, 133, 1331-1340 (1993)... 

Basu, S. and Wickstrom, E. (1997) Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake. Bioconj. Chem., 8, 481—488. 

Jansson, A., Meldal, M., and Bock, K. (1992) Solid-phase synthesis and characterization of O-dimannosylated heptadecapeptide analogues of human insulin-like growth factor 1 (IGF-1). J. Am. Chem. Soc. Perkin Trans I., 1699-1707. 

Figure 7.42. Model for regulation of AFP synthesis in winter flounder (Pleuronectes americanus). CNS central nervous system GHRH growth hormone releasing hormone GH growth hormone IGF-1 insulin-like growth factor-1 C/EBPa CCAAT enhancer binding protein a AEP antifreeze enhancerbinding protein. See text for details. Arrows with striped tails denote up-regulation or down-regulation.

In addition to these various actions on rather general metabolic functions, GH also has some very specific effects. It has a general stimulatory effect on protein synthesis but also stimulates synthesis of some proteins selectively. Predominant among these is somatomedin C/insulin-like growth factor I (Sm-C/IGF-I), production of which is stimulated markedly in many tissues, especially the liver [13,16]. 

The anterior pituitary releases GH in 6 to 8 pulsatile bursts over a 24 h period the major portion is released just prior to deep sleep. Its secretion is controlled by hypothalamic peptides GH-releasing hormone stimulates GH secretion, while somatostatin inhibits it. GH stimulates the synthesis of insulin-like growth factor-1 (IGF-1 somatomedin C) mainly, but not solely, in the liver. GH and IGF-1 receptors are widely scattered throughout the body, and both hormones exert important metabolic actions in various tissues, especially muscle and bone. 

Hormones. Zinc is thought to have a role in the synthesis and actions of many hormones, via zinc transcription factors. Zinc depletion is associated with low circulating concentrations of testosterone, free T4, insulin-like growth factor (IGF)-l, and thymulin. Both plasma IGE-1 and growth velocity increase in zinc-supplemented children. ... 

A recent case described the synthesis of more stable bioisosteres of inhibitors of the insulin-like growth factor-1 receptor kinase (Figure 15.43). Based on the structure of AG 538 ° which contains two catechol rings and is sensitive to oxidation in cell, a new series of kinase inhibitors were developed. The catechol moiety was replaced by a benzoxazolone ring resistant to oxidation yielding two compounds GB19 and AGL2263 which maintain same potency as AG 538. 

Acquaviva, A. M., Bruni, C. B., Nissley, S. P., and Rechler, M. M., Cell-free synthesis of rat insulin-like growth factor II. Diabetes 31, 656-658 (1982). 

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