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Abstract

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 C578L/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₊]<sub>i</sup>). 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₊]<sub>i</sup>) 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.