Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada; Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Rd. N., Mississauga, ON L5L 1C6, Canada.
Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada; Department of Cells and Systems Biology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada; Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Rd. N., Mississauga, ON L5L 1C6, Canada.
Front Neuroendocrinol. 2017 Jul;46:32-45. doi: 10.1016/j.yfrne.2017.04.003. Epub 2017 Apr 26.
Testicular androgens are the major endocrine factor promoting masculine phenotypes in vertebrates, but androgen signaling is complex and operates via multiple signaling pathways and sites of action. Recently, selective androgen receptor mutants have been engineered to study androgenic mechanisms of sexual differentiation of the nervous system and behavior. The focus of these studies has been to evaluate androgenic mechanisms within the nervous system by manipulating androgen receptor conditionally in neural tissues. Here we review both the effects of neural loss of AR function as well as the effects of neural overexpression of AR in relation to global AR mutants. Although some studies have conformed to our expectations, others have proved challenging to assumptions underlying the dominant hypotheses. Notably, these studies have called into question both the primacy of direct, neural mechanisms and also the linearity of the relationship between androgenic dose and sexual differentiation of brain and behavior.
睾丸激素是促进脊椎动物雄性表型的主要内分泌因素，但雄激素信号转导复杂，通过多种信号通路和作用部位发挥作用。最近，选择性雄激素受体突变体已被设计用于研究神经系统和行为的性分化的雄激素机制。这些研究的重点是通过在神经组织中条件性地操纵雄激素受体来评估神经系统内的雄激素机制。在这里，我们回顾了 AR 功能丧失的神经作用以及 AR 在与全局 AR 突变体相关的神经过度表达的神经作用。尽管一些研究符合我们的预期，但其他研究结果却对主导假设的基本前提提出了挑战。值得注意的是，这些研究不仅对直接的神经机制的首要性提出了质疑，而且对雄激素剂量与大脑和行为的性分化之间的线性关系提出了质疑。
