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Functional testosterone receptors in plasma membranes of T cells
Author(s) -
BENTEN W. Peter M.,
LIEBERHERR MICHELE,
GIESE GüNTER,
WREHLKE CHRISTIAN,
STAMM OLAF,
SEKERIS CONSTANTIN E.,
MOSSMANN HORST,
WUNDERLICH FRANK
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.1.123
Subject(s) - androgen receptor , receptor , chemistry , testosterone (patch) , cytosol , lncap , cytoplasm , flow cytometry , microbiology and biotechnology , extracellular , medicine , biology , endocrinology , biochemistry , cancer cell , prostate cancer , cancer , enzyme
T cells are considered to be unresponsive to testosterone due to the absence of androgen receptors (AR). Here, we demonstrate the testosterone responsiveness of murine splenic T cells in vitro as well as the presence of unconventional cell surface receptors for testosterone and classical intracellular AR. Binding sites for testosterone on the surface of both CD4 + and CD8 + subsets of T cells are directly revealed with the impeded ligand testosterone‐BSA‐FITC by confocal laser scanning microscopy (CLSM) and flow cytometry, respectively. Binding of the plasma membrane impermeable testosterone‐BSA conjugate induces a rapid rise (<5s) in[Ca 2+ ] i of Fura‐2‐loaded T cells. This rise reflects influx of extracellular Ca 2+ through non‐voltage‐gated and Ni 2+ ‐blockable Ca 2+ channels of the plasma membrane. The testosterone‐BSA‐induced Ca 2+ import is not affected by cyproterone, a blocker of the AR. In addition, AR are not detectable on the surface of intact T cells when using anti‐AR antibodies directed against the amino and carboxy terminus of the AR, although T cells contain AR, as revealed by reverse transcription‐polymerase chain reactions and Western blotting. AR can be visualized with the anti‐AR antibodies in the cytoplasm of permeabilized T cells by using CLSM, though AR are not detectable in cytosol fractions when using the charcoal binding assay with 3 H‐R1881 as ligand. Cytoplasmic AR do not translocate to the nucleus of T cells in the presence of testosterone, in contrast to cytoplasmic AR in human cancer LNCaP cells. These findings suggest that the classical AR present in splenic T cells are not active in the genomic pathway. By contrast, the cell surface receptors for testosterone are in a functionally active state, enabling T cells a nongenomic response to testosterone.—Benten, W. P. M., Lieberherr, M., Giese, G., Wrehlke, C., Stamm, O., Sekeris, C. E., Mossmann, H., Wunderlich, F. Functional testosterone receptors in plasma membranes of T cells. FASEB J. 13, 123–133 (1999)