Testosterone signaling in T cells and macrophages.
This review summarizes data about non-genomic actions of testosterone on murine malaria, T cells and macrophages produced by our group during the last 15 years. In C57BL/10 mice, testosterone induces a lethal outcome of blood stage infections with Plasmodium chabaudi which normally takes a self-healing course controlled by genes of the H-2 complex and the non-H-2 background. This suppressive effect of testosterone is mediated neither via the classic intracellular androgen receptor (AR) response nor, after conversion of testosterone to estradiol, via the estrogen receptor. Testosterone acts non-genomically, i.e. through surface receptors, on murine T cells and macrophages, which becomes evident as a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)). In T cells, this rise reflects predominantly influx of extracellular Ca(2+), while it is predominantly due to release of Ca(2+) from intracellular Ca(2+)-stores in macrophages. The testosterone-induced rise in [Ca(2+)](i) of both macrophages and T cells is not inhibited by the AR-blocker cyproterone, and it is also inducible by the plasma membrane impermeable ligand testosterone-BSA. The surface receptors initiate a transcription-independent signaling pathway of testosterone. Currently, we are trying to isolate testosterone surface receptors and to investigate a possible cross-talk of non-genomic testosterone signaling with other genotropic signaling pathways.
Wunderlich
Frank
F
Division of Molecular Parasitology, Heinrich-Heine-University, 40225 Duesseldorf, Germany. frank.wunderlich@uni-duesseldorf.de
Benten
W Peter M
WP
Lieberherr
Michèle
M
Guo
Zhiyong
Z
Stamm
Olaf
O
Wrehlke
Christian
C
Sekeris
Constantin E
CE
Mossmann
Horst
H
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008288:Malaria / Q000139:chemically induced / Q000401:mortality; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011944:Receptors, Androgen / Q000172:deficiency / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*
D011944:Receptors, Androgen; D011956:Receptors, Cell Surface; D013739:Testosterone