Psychology, University of Toronto Mississauga, Mississauga, ON, Canada.
Cells and Systems Biology, University of Toronto, Toronto, ON, Canada.
J Neuroendocrinol. 2017 Sep;29(9). doi: 10.1111/jne.12515.
The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic neuromuscular system in which the masculinisation of cell number is assumed to depend on the action of perinatal androgen in non-neural targets, whereas the masculinisation of cell size is assumed to depend primarily on the action of adult androgen on SNB cells themselves. To test these hypotheses, we characterised the SNB of Cre/loxP transgenic mice that overexpress androgen receptor (AR) throughout the body (CMV-AR) or in neural tissue only (Nestin-AR). Additionally, we examined the effects of androgen manipulation in male mutants and wild-type (WT) controls. We reproduced the expected sex differences in both motoneurone number and size, as well as the expected adult androgen dependence of SNB size. We found effects of genotype such that both Nestin-AR and CMV-AR have more SNB motoneurones than WT littermates and also that CMV-AR females have larger SNB motoneurones than Nes-AR or WT females. These results raise the possibility that AR can act in neurones and/or glia to rescue SNB motoneurones, as well as on non-neural AR to increase SNB cell size.
球海绵体神经核(SNB)是一种性别二态性的神经肌肉系统,其中细胞数量的男性化被认为取决于围产期雄激素对非神经靶标的作用,而细胞大小的男性化则被认为主要取决于成年雄激素对 SNB 细胞本身的作用。为了验证这些假设,我们对全身过表达雄激素受体(AR)(CMV-AR)或仅在神经组织中过表达 AR(Nestin-AR)的 Cre/loxP 转基因小鼠的 SNB 进行了特征描述。此外,我们还研究了雄激素处理对雄性突变体和野生型(WT)对照的影响。我们重现了预期的运动神经元数量和大小的性别差异,以及 SNB 大小的预期成年雄激素依赖性。我们发现了基因型的影响,即 Nestin-AR 和 CMV-AR 都比 WT 同窝仔鼠有更多的 SNB 运动神经元,而且 CMV-AR 雌性的 SNB 运动神经元比 Nes-AR 或 WT 雌性的更大。这些结果提出了一种可能性,即 AR 可以在神经元和/或神经胶质中发挥作用,以挽救 SNB 运动神经元,以及在非神经 AR 中增加 SNB 细胞大小。