title: The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients.
abstract: OBJECTIVE
  Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-I/IGFBP-3 ratio have been described following GH administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated in active acromegaly due to excessive GH secretion. However, the individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously.
  
  
  METHODS
  We studied this ratio in 198 healthy adults and in 56 acromegalic patients, grouped according to their serum GH levels (group I GH < 2mIU/l II GH 2-10 mIU/l; III GH > 10 mIU/l). In all subjects a single blood sample was drawn for IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In 38 of the patients a 24-hour urinary collection was performed for GH determination.
  
  
  RESULTS
  In healthy adults serum levels of IGF-I and IGFBP-3 decreased with increasing age (r = -0.52 and r = -0.34, respectively, P < 0.0001). In addition, the molar IGF-I/IGFBP-3 ratio declined with increasing age (r = -0.44, P = 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF-I was increased 7.97 standard deviations (SDS) and IGFBP-3 was increased 4.20 SDS (P < 0.0001). Serum levels of IGF-II were normal in all three groups (588 +/- 240 micrograms/l) whereas IGFBP-1 and IGFBP-2 levels were low and IGFBP-2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF-I/IGFBP-3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001).
  
  
  CONCLUSIONS
  We demonstrated a decreasing molar IGF-I/IGFBP-3 ratio with increasing age in healthy adults and an increased ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels in the acromegalic patients, we speculate that the molar ratio between IGF-I and IGFBP-3 reflects free (biologically active) IGF-I and is dependent on GH levels.
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University Hospital, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Juul
authors.forename: K
authors.initials: K
authors.lastname: Main
authors.forename: W F
authors.initials: WF
authors.lastname: Blum
authors.forename: J
authors.initials: J
authors.lastname: Lindholm
authors.forename: M B
authors.initials: MB
authors.lastname: Ranke
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkebaek
mesh_terms: D000172:Acromegaly / Q000097:blood*; D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood*; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone