Introduction: In this paper, the authors describe the role of Insulin-like growth binding factorfactorsPs) in regulating the availability of IGFs and in growth as well. AuthorThe authorsdedescribebout the specific cells that produce IGF-1 and ccomparethe different types of IGFBPs found in mammals and fish. This paper also describes the role of hormones and envirothe nment in the regulation of circulating IGFBPs in fish. Mainly, six IGFBPs are present in mammals in circulation and the activity is modulamodulated byus ways. IGFBP-1 inhibits the action of IGF by preventing it from interacting with its receptor.
Also, it shows dynamic fluctuations in response to meals and shows increman ent in the level under catabolic conditions like fasting. IGFBP-2 also inhibits the action of IGF-1 and their levels are high under catabolic conditions. IGFBP-3 and Acid liable substance (ALS) are produced in the liver by Kupffer and endothelial cells, and hepatocytes, respectively. IGFBP-3 is a major carrier of circulating IGF-1 by forma ing ternary complex with IGF and ALS in mammalian circulation.
IGFBPs can be detected by ligand blotting and binding assay in plasma/serum. Fish IGFBPs were reported in the circulation of four teleost species (coho salmon, Oncorhynchus kisutch; Striped bass, Moronesaxatilis; tilapia, Oreochromis mossambicus;long-jawedd mudsucker, (goby), Gillichthysmiabilis). IGFBPsweres detected in lamprey by using both ligand blotting and binding assay in the plasma which leads the researcher to hypothesize that IGFBP is an ancient protein family that emerged in the early history of vertebrates.
Results: Mainly, three major IGFBs have been detected in teleost ranging from 20-25, 28-32, and 40-50KDa, although identities are not well established.
The serum of salmon contains three IGFBPsat 41, 2,8, and 22kDaa that are identified through protein purification and cDNA cloning. Salmon 28- and 22-KDa are co-orthologs of IGFBP-1, designated as IGFBP -1a and IGFBP -1b. Salmon IGFBP 41 corresponds to IGFBP-2b of mammals. The ternary complex of IGFBP-3, IG, F, and ALS is vital for maintaining a high concentration of IGFs in the mammalian circulation. There is now any supportive evidence of the presence othe f ternary complex in fish circulation. The presence of ALS in fish circulation is not known and extremely low levels of production of IGFBP-3 by the liver (absence of Kupffer cells) in salmon might be the major reason for the lack of ternary cofactorsmplex in salmon circulation. Also, the capillary barrier in mammals has a molecular cutoff of around 60 KDa, which doesn’t allow the 150 KDa ternary complex to pass through.
However, fish capillaries are relatively “leaky” lacking a clear molecular cutoff, and hence even if the ternary complex is formed, IGFs may not be sequestered in the circulation.
The circulation of IGFBPs in fish blood is under the control of several hormones (GH, insulin, glucocorticoids, testosterone, etc) and growth factors (epidermal growth factor and IGF-1). Insulin treatment in mammals inhibits IGFBP-1 both at the mRNA and protein levels. To support this statement in fish, the isletoctomized goby showed induction of 24- and 30-KDa IGFBPs in plasma and restored to basal conditions after the treatment of Insulin. However, this was not true in the case of salmon. Thus, it can be concluded that the inhibitory effect of insulin may be species-specific or indirect in fish. Catabolic conditions like fasting, splenectomy, or handling stress increase the level of low-molecular-weight IGFBPs when cortisol is also elevated.IGFBP-1a and IGFBP-1b are inducible by exogenous cortisol in rainbow trout. GH treatment increases the circulation of IGFBP-2b in salmon like mammalian IGFBP-3. Environmental factor controls the circulating levels of IGFBPs. IGFBP-2b in salmon is sensitive to nutritional conditions including fasting and feeding rations. The effects of increase or decrease in water temperature on circulating different types of IGFBPs are different among GFBPs types. Smoltification activates several endocrine axes like the GH-IGF-I system and it causes changes in IGFBPs during this period. IGFBP-2b reaches a peak level in Coho salmon one month earlier than IGFBP-1b during smoltification at the end of March. In some fish, plasma IGF-I showed two peaks in late March and late April corresponding to peaks of IGFBP-2b and -1b, respectively suggesting that IGFBPs play different roles during smoltification.
Critical review: I had several issues that I would like to mention in this review paper. More elaboration should have been done on the methodology. The relative abundance and affinity reflect the intensity of the band to the IGF used as a ligand, care should be taken when comparing different types of IGFBPs. It would have been clear if the problem has been mentioned in it. When comparing ternary complex, binary and free IGFBPs, the reasons need to be mentioned why the concentration of IGFBPsdecreases when volume increases.