Liu L, Zhao Y, Wang Y, Li Q, Wang Z, Wang L, Qiao Z
Medical School, Shanghai Jiaotong University, Huashanlu, Shanghai, People's Republic of China.
Methods Find Exp Clin Pharmacol. 2005 Nov;27(9):623-8. doi: 10.1358/mf.2005.27.9.939336.
The biological activity of testosterone is thought to occur predominantly through binding to the androgen receptor (AR), a member of the nuclear receptor superfamily that functions as a ligand-activated transcription factor. Here, we found that testosterone could induce a rapid rise in the intracellular free Ca2+ concentration ([Ca2+]i) of Fura-2 loaded bone marrow-derived macrophages (BMMs), which was found to be predominantly due to the influx of extracellular Ca2+ through Ni2+-blockable Ca2+ channels in the plasma membrane. However, these effects of testosterone could not be associated with the classical intracellular AR in BMMs, since AR was not detectable using different experimental techniques. Instead, it was found that testosterone could bind to the surface of BMMs by the use of an impermeable testosterone-BSA-FITC, and Ca2+ influx could also be induced by testosterone conjugated to BSA. Our data indicated a novel mode of direct action of testosterone on BMMs, which was not mediated through the classical AR response, but through the binding sites of testosterone on cell surfaces.
睾酮的生物活性被认为主要是通过与雄激素受体（AR）结合来实现的，AR是核受体超家族的成员，作为一种配体激活的转录因子发挥作用。在此，我们发现睾酮可诱导负载Fura-2的骨髓来源巨噬细胞（BMMs）的细胞内游离Ca2+浓度（[Ca2+]i）迅速升高，这主要是由于细胞外Ca2+通过质膜中Ni2+可阻断的Ca2+通道内流所致。然而，睾酮的这些作用与BMMs中经典的细胞内AR无关，因为使用不同的实验技术均未检测到AR。相反，通过使用不可渗透的睾酮-BSA-FITC发现睾酮可与BMMs表面结合，并且与BSA偶联的睾酮也可诱导Ca2+内流。我们的数据表明睾酮对BMMs有一种新的直接作用模式，该模式不是通过经典的AR反应介导的，而是通过睾酮在细胞表面的结合位点介导的。
