Insulin-like growth factor-1 (IGF-1) is a protein with a role in growth hormone- (GH) induced signaling, development and other functions1. For example, the IGF-1 levels of some mammalian species change in response to feeding and changes in the amounts of food-generated energy2. IGF-1 is regarded as a peptide hormone, an endocrine factor and a paracrine factor, depending on the part of the body in which it is active3. It is available as a laboratory-grade compound known as IGF-1 LR3. This synthetic analog of IGF-1 has an arginine residue in place of the normal glutamic acid in the third position along its sequence. IGF-1 LR3 also has an elongated amino-terminus, to give a protein of 83 amino acids as opposed to the 70 found in the natural or endogenous molecule. These variations impair the ability of IGF-binding proteins (IGFBP) in vivo or in vitro1. IGFBPs are involved in the regulation of IGF-1 and its activity at the IGF receptor. Therefore, IGF-1 LR3 may be more potent when administered in comparison to normal IGF-11. On the other hand, it may also have greater clearance from the blood due to the lack of binding. The affinity of IGF-1 for the IGF receptor is poor compared to that of IGFBPs for IGF-11. Therefore, binding proteins can exert considerable negative regulation on IGF receptor activation. (Conversely, some IGFBP subtypes promote IGF-1 activity, depending on a number of factors including their phosphorylation status1.) Modified IGF can have a 100-fold (or more) reduction in affinity for IGFBPs compared to the original molecule1. IGF-1 LR3 may have a potency that is approximately two-fold greater than that of IGF-1, as evidenced by a study using rats4. IGF-1 has a molecular weight of about 7kDa; IGF-1 LR3 may be a little larger than this4.
Treatment with IGF-1 LR3 is associated with significant increases in sodium ion flux across the gut epithelium of sheep2. This indicates a role for IGF-1 in the essential nerve cell activity, motility and pH regulation in the digestive tract. IGF-1 LR3 has also been used to assess the role of IGF-1 in follicle development in mammals. Both IGF-1 LR3 and recombinant human IGF-1 were associated with dose-dependent increases in the size and estradiol release of cultured bovine follicles5. However, higher doses of IGF-1 resulted in reduced oocyte numbers, indicating that follicular development depends on the tight regulation of IGF-1 activity5. This may be supported by the detection of IGFBP2 and of IGFBP3 mRNA in the cultured follicles5. IGF-1 LR3 may also be used to assess the overexpression of IGF receptors often observed in tumor cells6. It is associated with cyclin D1 activity, a marker of cell cycle activity, mediated by the IGF receptor in these cells6. The function of this is to enhance the proliferation, survival and invasive migration of tumors6. IGF-1 LR3 may also be applied to studies assessing novel antagonists of this receptor intended to prevent this. Another function of IGF-1 LR3 is to assess the expression patterns of IGFBPs in various tissues. For example, a recent study found that these are not regulated by the presence of IGF in murine skeletal muscle7.
References:
- Mohan S, Baylink DJ. IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms. The Journal of endocrinology. 2002;175(1):19-31.
- Shen Z, Martens H, Schweigel-Rontgen M. Na+ transport across rumen epithelium of hay-fed sheep is acutely stimulated by the peptide IGF-1 in vitro. Experimental physiology. 2012;97(4):497-505.
- Brankin V, Mitchell MR, Webb B, Hunter MG. Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro. Reproductive biology and endocrinology : RB&E. 2003;1:55.
- Tomas FM, Lemmey AB, Read LC, Ballard FJ. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. The Journal of endocrinology. 1996;150(1):77-84.
- Thomas FH, Campbell BK, Armstrong DG, Telfer EE. Effects of IGF-I bioavailability on bovine preantral follicular development in vitro. Reproduction (Cambridge, England). 2007;133(6):1121-1128.
- Haluska P, Carboni JM, Loegering DA, et al. In vitro and in vivo antitumor effects of the dual insulin-like growth factor-I/insulin receptor inhibitor, BMS-554417. Cancer research. 2006;66(1):362-371.
- Oliver WT, Rosenberger J, Lopez R, Gomez A, Cummings KK, Fiorotto ML. 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. Endocrinology. 2005;146(12):5455-5462.