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J. Biol. Chem., Vol. 276, Issue 27, 24760-24766, July 6, 2001
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From the Department of Pathology and Laboratory Medicine,
University of Pennsylvania Medical Center,
Philadelphia, Pennsylvania 19104
The actions of prolactin (PRL) are mediated by
its receptor, a member of the superfamily of single transmembrane
cytokine receptors. High affinity binding proteins for the closely
related growth hormone have been found in the sera of several
species including humans and are generated by alternative splicing or proteolysis of the growth hormone receptor extracellular domain (ECD).
In contrast, no conclusive evidence has been presented that an
analogous prolactin-binding protein (PRLBP) is expressed in human
serum. Using both monoclonal and polyclonal antibodies generated
against hPRL and the ECD of the human prolactin receptor, co-immunoprecipitation analyses of human serum identified a 32-kDa hPRLBP capable of binding both hPRL and human growth hormone. A
measurable fraction of circulating PRL (36%) was associated with the
hPRLBP. Despite well documented sex differences in serum hPRL levels,
there were no significant differences in the levels of hPRLBP found in
the sera of normal adult males and females (15.3 ± 1.3 ng/ml
versus 13.4 ± 0.8 ng/ml, respectively (mean ± S.E.)). Immunoprecipitation studies also detected the PRLBP in human
milk albeit at lower concentrations than found in sera. Deglycosylation
did not alter its electrophoretic mobility, indicating an absence of
carbohydrate moieties and suggesting that the hPRLBP spans most of the
PRLR ECD, a result confirmed by limited proteolysis and mass
spectrometry. The potential function of this serum chaperone was
assessed in vitro by the addition of recombinant hPRLBP to the culture medium of the PRL-dependent Nb2 T-cell line.
These studies revealed that the hPRLBP antagonizes PRL action,
inhibiting PRL-driven growth in a dose-dependent manner.
Identification and Characterization of the
Prolactin-binding Protein in Human Serum and Milk*
*
This study was supported in part by Grants 2R01CA69294 (to
C. V. C.) and 1F32DK09727 (to J. B. K.) from the National
Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Pathology and
Laboratory Medicine, University of Pennsylvania Medical Center, 513 Stellar-Chance Laboratories, 422 Curie Blvd., Philadelphia, PA
19104. E-mail: clevengc@mail.med.upenn.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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