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Vol. 10, Issue 10, 3113-3123, October 1999
*Division of Molecular Parasitology and Centre of
Biological-Medical Research, Heinrich-Heine-University, 40225 Duesseldorf, Germany; and 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.
Centre National de la Recherche
Scientifique, Unité Propre de Recherche 1524, Institut
National de la Recherche Agronomique, 78352 Jouy-en-Josas,
France
Corresponding author. E-mail address:
frank.wunderlich{at}uni-duesseldorf.de.
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