Forger N G
Department of Psychology and Center for Neuroendocrine Studies, University of Massachusetts, Amherst, MA 01003, USA.
J Neuroendocrinol. 2009 Mar;21(4):393-9. doi: 10.1111/j.1365-2826.2009.01825.x.
The hormonal control of cell death is currently the best-established mechanism for creating sex differences in cell number in the brain and spinal cord. For example, males have more cells than do females in the principal nucleus of the bed nucleus of the stria terminalis (BNSTp) and spinal nucleus of the bulbocavernosus (SNB), whereas females have a cell number advantage in the anteroventral periventricular nucleus (AVPV). In each case, the difference in cell number in adulthood correlates with a sex difference in the number of dying cells at some point in development. Mice with over- or under-expression of cell death genes have been used to test more directly the contribution of cell death to neural sex differences, to identify molecular mechanisms involved, and to determine the behavioural consequences of suppressing developmental cell death. Bax is a pro-death gene of the Bcl-2 family that is singularly important for apoptosis in neural development. In mice lacking bax, the number of cells in the BNSTp, SNB and AVPV are significantly increased, and sex differences in total cell number in each of these regions are eliminated. Cells rescued by bax gene deletion in the BNSTp express markers of differentiated neurones and the androgen receptor. On the other hand, sex differences in other phenotypically identified populations, such as vasopressin-expressing neurones in the BNSTp or dopaminergic neurones in AVPV, are not affected by either bax deletion or bcl-2 over-expression. Possible mechanisms by which testosterone may regulate cell death in the nervous system are discussed, as are the behavioural effects of eliminating sex differences in neuronal cell number.
目前，激素对细胞死亡的控制是在大脑和脊髓细胞数量上产生性别差异的最成熟机制。例如，在终纹床核主核（BNSTp）和球海绵体肌脊髓核（SNB）中，雄性的细胞比雌性多，而在室旁前腹侧核（AVPV）中，雌性的细胞数量占优势。在每种情况下，成年期细胞数量的差异都与发育过程中某个时间点死亡细胞数量的性别差异相关。已使用细胞死亡基因过表达或低表达的小鼠来更直接地测试细胞死亡对神经性别差异的影响，确定其中涉及的分子机制，并确定抑制发育性细胞死亡的行为后果。Bax是Bcl-2家族的一个促死亡基因，对神经发育中的细胞凋亡尤为重要。在缺乏bax的小鼠中，BNSTp、SNB和AVPV中的细胞数量显著增加，并且这些区域中总细胞数量的性别差异被消除。在BNSTp中通过bax基因缺失挽救的细胞表达分化神经元和雄激素受体的标志物。另一方面，其他表型确定的群体中的性别差异，如BNSTp中表达加压素的神经元或AVPV中的多巴胺能神经元，不受bax缺失或bcl-2过表达的影响。文中讨论了睾酮可能调节神经系统细胞死亡的潜在机制，以及消除神经元细胞数量性别差异的行为影响。
