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Originally published In Press as doi:10.1074/jbc.M202495200 on May 15, 2002
J. Biol. Chem., Vol. 277, Issue 29, 26618-26622, July 19, 2002
Sex Hormone-binding Globulin in the Human Prostate Is Locally
Synthesized and May Act as an Autocrine/Paracrine Effector*
Daniel J.
Hryb ,
Atif M.
Nakhla ,
Scott M.
Kahn §,
Jonathan
St. George,
Nomi C.
Levy,
Nicholas A.
Romas§, and
William
Rosner ¶
From the Departments of Medicine and
§ Urology, St. Luke's/Roosevelt Hospital
Center, and College of Physicians and Surgeons, Columbia University,
New York, New York 10019
Sex hormone-binding globulin (SHBG) is a
plasma protein synthesized and secreted by the liver. Its initial
description stemmed from its ability to bind estrogens and androgens
and its capacity to regulate the free concentration of the
steroids that bind to it. Additionally, it participates in signal
transduction for certain steroid hormones at the cell membrane. It
binds with high affinity to a specific membrane receptor
(RSHBG) in prostate stromal and epithelial cells,
wherein the SHBG·RSHBG complex forms. An
appropriate steroid binds to this complex and results in increases of
intracellular cAMP. These two disparate functions of SHBG, regulation
of the concentration of free steroids in plasma and signal transduction in selected tissues, raise the question of how its synthesis and secretion might be regulated so as to best perform these two disparate functions. In this paper we demonstrate that SHBG is produced in human
prostate cancer cell lines (LNCaP, DU 145, and PC 3) as well as in
cultured human prostate epithelial and stromal cells. In addition, in
tissue sections of human prostate, we demonstrate the presence of SHBG
(immunocytochemistry) and SHBG mRNA (in situ hybridization). These observations are consistent with the hypothesis that SHBG, destined to participate in signaling at the cell membrane, is locally regulated and produced.
*
This work was supported in part by grants from the Starr
Foundation and the Lowey Family Foundation.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.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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