Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma

J Clin Endocrinol Metab. 1992 Oct;75(4):1046-53. doi: 10.1210/jcem.75.4.1383255.


Insulin-like growth factor binding protein-3 (IGFBP-3), the major serum carrier protein for the IGFs, is absent from Western ligand blots of seminal plasma, but is detectable by RIA. IGFBP-3 protease activity has recently been described in pregnancy serum. We investigated the possibility that seminal plasma contains an IGFBP-3 protease, by incubating seminal plasma with 125I-labeled human IGFBP-3. Seminal plasma was found to have potent IGFBP-3 protease activity with a cleavage pattern different from that of pregnancy serum. Prostate-specific antigen (PSA) is a serine protease found in semen. Autoradiographs measuring IGFBP-3 protease activity demonstrated that purified PSA cleaved IGFBP-3, yielding a cleavage pattern identical to that of seminal plasma. IGFBP-2 and -4 in seminal plasma were not degraded by PSA. Cleavage of IGFBP-3 by PSA resulted in a marked reduction in the binding affinity of the fragments to IGF-I, but not IGF-II. We speculate that PSA may serve to modulate IGF function within the reproductive system or in prostate cancer by altering IGF-IGFBP-3 interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoradiography
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Insulin-Like Growth Factor Binding Proteins
  • Male
  • Precipitin Tests
  • Prostate-Specific Antigen / metabolism*
  • Semen / enzymology*
  • Somatomedins


  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Somatomedins
  • Prostate-Specific Antigen