Knoll John Gabriel, Wolfe Cory A, Tobet Stuart A
Department of Biomedical Sciences, Colorado State University, 1617 Campus Delivery, Fort Collins, CO 80523, USA.
Eur J Neurosci. 2007 Sep;26(5):1091-9. doi: 10.1111/j.1460-9568.2007.05751.x.
The preoptic area-anterior hypothalamus (POA-AH) is characterized by sexually dimorphic features in a number of vertebrates and is a key region of the forebrain for regulating physiological responses and sexual behaviours. Using live-cell fluorescence video microscopy with organotypic brain slices, the current study examined sex differences in the movement characteristics of neurons expressing yellow fluorescent protein (YFP) driven by the Thy-1 promoter. Cells in slices from embryonic day 14 (E14), but not E13, mice displayed significant sex differences in their basal neuronal movement characteristics. Exposure to 10 nm estradiol-17beta (E2), but not 100 nm dihydrotestosterone, significantly altered cell movement characteristics within minutes of exposure, in a location-specific manner. E2 treatment decreased the rate of motion of cells located in the dorsal POA-AH but increased the frequency of movement in cells located more ventrally. These effects were consistent across age and sex. To further determine whether early-developing sex differences in the POA-AH depend upon gonadal steroids, we examined cell positions in mice with a disruption of the steroidogenic factor-1 gene, in which gonads do not form. An early-born cohort of cells were labelled with the mitotic indicator bromodeoxyuridine (BrdU) on E11. More cells were found in the POA-AH of females than males on the day of birth (P0) regardless of gonadal status. These results support the hypothesis that estrogen partially contributes to brain sexual dimorphism through its influence on cell movements during development. Estrogen's influence may be superimposed upon a pre-existing genetic bias.
视前区-下丘脑前部（POA-AH）在许多脊椎动物中具有性别二态性特征，是前脑调节生理反应和性行为的关键区域。本研究使用活细胞荧光视频显微镜和脑片培养技术，检测了由Thy-1启动子驱动表达黄色荧光蛋白（YFP）的神经元运动特征的性别差异。来自胚胎第14天（E14）而非E13小鼠的脑片细胞，在基础神经元运动特征上表现出显著的性别差异。暴露于10 nM的17β-雌二醇（E2）而非100 nM的双氢睾酮，在暴露数分钟内以位置特异性方式显著改变了细胞运动特征。E2处理降低了位于背侧POA-AH的细胞的运动速率，但增加了位于更腹侧的细胞的运动频率。这些效应在年龄和性别上是一致的。为了进一步确定POA-AH中早期出现的性别差异是否依赖于性腺类固醇，我们检测了类固醇生成因子-1基因缺失的小鼠的细胞位置，这些小鼠不形成性腺。在E11用有丝分裂标记物溴脱氧尿苷（BrdU）标记了一组早期出生的细胞。无论性腺状态如何，出生当天（P0）在雌性小鼠的POA-AH中发现的细胞比雄性小鼠更多。这些结果支持了这样的假设，即雌激素通过其在发育过程中对细胞运动的影响部分促成了脑的性别二态性。雌激素的影响可能叠加在预先存在的遗传偏倚之上。
