Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma.
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.
Cohen
P
P
Department of Pediatrics, Stanford University Medical Center, California 94305.
Graves
H C
HC
Peehl
D M
DM
Kamarei
M
M
Giudice
L C
LC
Rosenfeld
R G
RG
D001345:Autoradiography; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D008297:Male; D011233:Precipitin Tests; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D012661:Semen / Q000201:enzymology*; D013002:Somatomedins
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D017430:Prostate-Specific Antigen