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Mol. Biol. Cell 10 (10): 3113-3123

Copyright © 1999 by The American Society for Cell Biology.

Vol. 10, Issue 10, 3113-3123, October 1999

Testosterone Signaling through Internalizable Surface Receptors in Androgen Receptor-free Macrophages

W. Peter M. Benten,* Michèle Lieberherr,dagger Olaf Stamm,* Christian Wrehlke,* Zhiyong Guo,* and Frank Wunderlich*Dagger

 *Division of Molecular Parasitology and Centre of Biological-Medical Research, Heinrich-Heine-University, 40225 Duesseldorf, Germany; and  dagger Centre National de la Recherche Scientifique, Unité Propre de Recherche 1524, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas, France

Testosterone acts on cells through intracellular transcription-regulating androgen receptors (ARs). Here, we show that mouse IC-21 macrophages lack the classical AR yet exhibit specific nongenomic responses to testosterone. These manifest themselves as testosterone-induced rapid increase in intracellular free [Ca2+], which is due to release of Ca2+ from intracellular Ca2+ stores. This Ca2+ mobilization is also inducible by plasma membrane-impermeable testosterone-BSA. It is not affected by the AR blockers cyproterone and flutamide, whereas it is completely inhibited by the phospholipase C inhibitor U-73122 and pertussis toxin. Binding sites for testosterone are detectable on the surface of intact IC-21 cells, which become selectively internalized independent on caveolae and clathrin-coated vesicles upon agonist stimulation. Internalization is dependent on temperature, ATP, cytoskeletal elements, phospholipase C, and G-proteins. Collectively, our data provide evidence for the existence of G-protein-coupled, agonist-sequestrable receptors for testosterone in plasma membranes, which initiate a transcription-independent signaling pathway of testosterone.

Dagger    Corresponding author. E-mail address: frank.wunderlich{at}

Molecular Biology of the Cell
Vol. 10, 3113-3123, October 1999
Copyright © 1999 by The American Society for Cell Biology

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