IGF-I, also known as somatomedin C, is a 7.6 kDa, 70 amino acid residue peptide, which mediates the actions of growth hormone (GH).1 IGF-I is synthesized as a prohormone, a polypeptide consisting of A, C, B, D, and E domains.1,2 After post-translational modification, the mature IGF-I consists of the A, C, B and D domains, and is structurally homologous to IGF-II and insulin. In vivo, IGF-I is secreted by the liver and several other tissues and is postulated to have mitogenic and metabolic actions at or near the sites of synthesis; this has been termed the paracrine role of IGF-I.1 IGF-I also appears in the peripheral circulation where it circulates primarily in a high molecular weight tertiary complex with IGF-binding protein-3 (IGFBP-3) and acid-labile subunit (ALS).2,3 A smaller proportion of IGF-I may circulate in association with other IGF-binding proteins.3 It has been estimated that <5% of plasma IGF-I circulates unbound.4 In vivo synthesis of IGF-I is stimulated by GH, and is also dependent on other factors, including adequate nutrition.1,5 IGF-I may inhibit pituitary production of GH; however, a feedback mechanism has not been completely defined.

In humans, plasma IGF-I levels are low during fetal and neonatal life, increase gradually during childhood, peak during mid-puberty, and decline gradually through adult life.1,5-7 Average plasma IGF-I levels are slightly higher in females at each age. Maternal plasma levels increase during pregnancy.1 Plasma IGF-I levels are stabilized by the IGF-binding proteins and there is negligible diurnal variation.5 Plasma IGF-I levels are low relative to age- and sex-related norms in GH deficiency5-7, malnutrition5,8 and in the syndrome of GH-receptor deficiency (Laron dwarfism).9 Abnormally low levels of plasma IGF-I have been used as a diagnostic indicator of GH deficiency, although a significant proportion of GH-deficient children may have IGF-I levels in the normal range, and normal short children may have low IGF-I levels.1,6,7 Plasma IGF-I levels may also be used to monitor the short- and long-term in vivo responses to GH treatment.5 Abnormally elevated IGF-I levels in acromegaly (GH excess) may be used as a diagnostic tool and to monitor treatment.1,5

Assay of plasma IGF-I is complicated by the presence of IGF-binding proteins, which may sequester IGF-I in the reaction mixture.1 Various methods have been devised to separate the IGF and IGF-binding proteins prior to assay. Size-exclusion gel chromatography in acid is considered to be optimal1,10, but this procedure is not feasible for routine use. Acidification followed by ethanol precipitation of the IGFBP fraction1,11 gives results which are similar to acid-chromatography. SepPak C-18 cartridges are less convenient11 and give variable results and relatively low recovery.

The Ansh Labs Total Rat/Mouse IGF-I Assay uses an acidification and neutralization method to dissociate IGF-I from all the binding proteins. IGF-I levels are quantified in the extracted samples using a highly sensitive and specific enzyme-linked immunosorbent assay.

References:
1. Daughaday E, Rotwein P: Insulin like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum and tissue concentrations. Endocrine Rev 10:68-91, 1989.
2. Baxter RC, Martin JL, Beniac VA: High molecular weight insulin-like growth factor binding protein complex. J Biol Chem 264:11843-11848, 1989.
3. Rechler M: Insulin-like growth factor binding proteins. Vit Horm 47:1-114, 1993.
4. Zapf J, Hauri C, Waldvogel M, Froesch ER: Acute metabolic effects and half-lives of intravenously administered insulin-like growth factors I and II in normal and hypophysectomized rats. J Clin Invest 77:1768-1775, 1986.
5. Lee PDK, Rosenfeld RG: Clinical utility of insulin-like growth factor assays. Pediatrician 14:154-161, 1987.
6. Rosenfeld RG, Wilson DM, Lee PDK, Hintz RL: Insulin-like growth factors I and II in evaluation of growth retardation. J Pediatr 109:428-433, 1986.
7. Lee PDK, Wilson DM, Rountree L, Hintz RL, Rosenfeld RG: Efficacy of insulin-like growth factor I levels in predicting the response to provocative growth hormone testing. Pediatr Res 27:45-51, 1990.
8. Soliman AT, Hassan AEHI, Aref MK, Hintz RL, Rosenfeld RG, Rogol AD: Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-calorie malnutrition before and after nutritional rehabilitation. Pediatr Res 20:1122-1130, 1986.
9. Guevara-Aguirre J, Rosenbloom AL, Fielder PJ, Diamond FB. Jr, Rosenfeld RG: Growth hormone receptor deficiency in Ecuador: Clinical and biochemical phenotype in two populations. J Clin Endocrinol Metab 76:417-423, 1993.
10. Powell DR, Rosenfeld RG, Baker BK, Liu F, Hintz RL: Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor I (IGF-I) and IGF-II in acid-chromatographed uremic serum. J Clin Endocrinol Metab 63:1186-1192, 1986.
11. Underwood LE, Murphy MG: Radioimmunoassay of the somatomedins. IN Patrono C (ed): Radioimmunoassay in Basic and Clinical Pharmacology (Handbook of Experimental Pharmacology vol 82) Springer-Verlag, Heidelberg, 1987, pp 561-574.
12. HHS Publication, 5th ed., 2007. Biosafety in Microbiological and Biomedical Laboratories. Available http://www.cdc.gov/biosafety/publications/bmbl5/BMBL5
13. DHHS (NIOSH) Publication No. 78–127, August 1976. Current Intelligence Bulletin 13 – Explosive Azide Hazard. Available http:// www.cdc.gov/niosh.
14. Kricka L. Interferences in immunoassays – still a threat. Clin Chem 2000; 46: 1037–1038.

Fujimoto M, Andrew M, Liao L, Zhang D, Yildirim G, Sluss P, Kalra B, Kumar A, Yakar S, Hwa V, Dauber A. Low IGF-I Bioavailability Impairs Growth and Glucose Metabolism in a Mouse Model of Human PAPPA2 p.Ala1033Val Mutation. Endocrinology. 2019 Jun 1;160(6):1363-1376. doi: 10.1210/en.2018-00755.

All Products Cited: IGF-I Free (Rat/Mouse) ELISA AL-136; IGF-I (Total) (Rat/Mouse) ELISA AL-137; IGFBP-3 (Intact) ELISA AL-149

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