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Prostate‐specific antigen triggers transformation of seminal α2‐macroglobulin (α2‐M) and its binding to α2‐macroglobulin receptor/low‐density lipoprotein receptor‐related protein (α2‐M‐R/LRP) on human spermatozoa
Author(s) -
Birkenmeier Gerd,
Usbeck Elke,
Schäfer Angelika,
Otto Andreas,
Glander HansJürgen
Publication year - 1998
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19980901)36:4<219::aid-pros2>3.0.co;2-a
Subject(s) - macroglobulin , receptor , ldl receptor , endocrinology , medicine , lipoprotein , prostate specific antigen , antigen , chemistry , biology , prostate , immunology , cholesterol , cancer
BACKGROUND The aim of this study was to identify the proteolytic activity which triggers the transformation of human α2‐macroglobulin (α2‐M) in seminal fluid and its binding to its receptor. METHODS Measurement of the concentrations of total and transformed α2‐M in seminal fluid was accomplished by ELISA. Zymography of seminal plasma was performed in SDS‐polyacrylamide gels containing casein as proteolytic substrate. Rate electrophoresis, SDS‐PAGE, and Western blotting were applied to study the complex formation of prostate‐specific antigen (PSA) with α2‐M. Ligand‐binding analysis of sperm cells was performed using [ 125 I]‐labeled proteins. Detection of receptor on sperm cells was achieved by immunofluorescence. RESULTS The mean concentration of total α2‐M in a random collection of seminal plasma was 4.6 μg/ml. On average, between 33–98% of the inhibitor was found to be transformed. Zymography of seminal plasma revealed a proteolytic activity which is associated with a 33‐kDa protein identified as PSA. Its proteolytic activity could be inhibited by α2‐M. Both purified PSA and seminal plasma were capable of transforming native α2‐M. Binding of PSA to α2‐M triggers the exposition of receptor binding sites in the inhibitor molecule, which causes binding of the complex to α2‐M‐R/LRP identified on spermatozoa. CONCLUSIONS PSA, the main proteinase in seminal fluid, is responsible for the transformation of α2‐M and for its binding to α2‐M‐R/LRP present on spermatozoa. The binding of α2‐M‐PSA complexes to the spermatozoa receptor may exert an impact on normal sperm‐cell functions. Prostate 36:219–225, 1998. © 1998 Wiley‐Liss, Inc.