Insulin-like growth factors (IGF-I, free IGF-I and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, IGFBP-3, IGFBP-6, and ALS) in blood circulation

J Clin Lab Anal. 1999;13(4):166-72. doi: 10.1002/(SICI)1098-2825(1999)13:4<166::AID-JCLA5>3.0.CO;2-X.


Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) play an important role in cell growth and differentiation. Clinical and epidemiological studies have indicated that measuring IGFs and IGFBPs in blood has potential implications in assessing growth-related abnormalities and risks of certain types of cancer. To facilitate the application, we reported a large collection of reference ranges of IGFs and IGFBPs in normal population and evaluations of these molecules in serum and plasma as well as the impact of freeze-thaw cycles on the measurement. IGF-I, IGFBP-3 andALS showed a similar pattern of change associated with age. Levels of these molecules were low at birth and increased with age through puberty. After puberty the levels declined slowly with age. Overall, IGF-I, IGFBP-3 and ALS were slightly higher in females than in males. Free IGF-I accounted for about 1% of the total IGF-I and its variation with age was similar to total IGF-I. IGF-II levels were also increased with age from birth to puberty, but became stable after puberty. There was little difference in IGF-II levels between genders. IGFBP-2 levels declined with age from birth to puberty. Levels of IGFBP-6 in contrast were increased with age. These IGF binding proteins were higher in males than in females. IGFs, IGFBP-3 and ALS were 5-10% higher in serum than in plasma. IGFBP-2 and IGFBP-6 differed substantially between serum and plasma. Freeze-thaw treatment up to five cycles had little impact on plasma levels of IGFs and IGFBP-3. Our observations suggest that levels of IGFs and their binding proteins are varied with age, gender, and types of specimen and that these variations need to be taken into consideration when IGFs and their binding proteins are utilized in clinic and research.

MeSH terms

  • Adult
  • Blood Circulation*
  • Blood Proteins / metabolism
  • Carrier Proteins / blood
  • Female
  • Glycoproteins / blood
  • Humans
  • Immunoassay
  • Insulin-Like Growth Factor Binding Protein 2 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Protein 6 / blood
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / analysis
  • Male
  • Middle Aged
  • Protein Binding
  • Receptors, Somatomedin / blood*
  • Reference Values
  • Somatomedins / analysis*


  • Blood Proteins
  • Carrier Proteins
  • Glycoproteins
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 6
  • Receptors, Somatomedin
  • Somatomedins
  • insulin-like growth factor binding protein, acid labile subunit
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II