Graduate Program in Neuroscience, University of California, San Francisco, MC2722, San Francisco, CA 94158, USA.
Neuron. 2010 Apr 29;66(2):260-72. doi: 10.1016/j.neuron.2010.03.024.
Testosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior remains to be established. Circulating testosterone activates the androgen receptor (AR) and also serves as the source of estrogen in the brain. We have used a genetic strategy to delete AR specifically in the mouse nervous system. This approach permits us to determine the function of AR in sexually dimorphic behaviors in males while maintaining circulating testosterone levels within the normal range. We find that AR mutant males exhibit masculine sexual and territorial displays, but they have striking deficits in specific components of these behaviors. Taken together with the surprisingly limited expression of AR in the developing brain, our findings indicate that testosterone acts as a precursor to estrogen to masculinize the brain and behavior, and signals via AR to control the levels of male behavioral displays.
睾酮和雌激素对脊椎动物的雄性行为至关重要。这两种信号通路如何相互作用来控制大脑和行为的雄性化仍有待确定。循环中的睾酮激活雄激素受体(AR),也作为大脑中雌激素的来源。我们使用了一种遗传策略来特异性地在小鼠神经系统中删除 AR。这种方法使我们能够确定 AR 在雄性中性别二态性行为中的功能,同时将循环中的睾酮水平维持在正常范围内。我们发现,AR 突变雄性表现出雄性的性行为和领地行为,但在这些行为的特定成分上存在显著缺陷。与 AR 在发育中的大脑中的表达非常有限相结合,我们的发现表明,睾酮作为雌激素的前体来使大脑和行为雄性化,并通过 AR 信号来控制雄性行为表现的水平。