Horvath T L, Wikler K C
Department of Obstetrics and Gynecology, Yale University, School of Medicine, New Haven, CT 06510, USA.
J Neuroendocrinol. 1999 Feb;11(2):77-84. doi: 10.1046/j.1365-2826.1999.00285.x.
Sex differences in the rat brain are dependent, in part, on oestrogen exposure during specific developmental perinatal periods. The availability of oestrogen requires precursor androgen and the presence of intraneuronal aromatase. To examine sites of oestrogen formation and action in the brain, immunocytochemical and biochemical localization of aromatase in the rat brain were determined between embryonic day 14 and postnatal day 20. Aromatase-immunolabelled neuronal profiles were present in hypothalamic, cortical and limbic regions. Surprisingly, aromatase immunoreactivity was also observed in non-limbic regions of the immature brain where it was previously unsuspected. Among these regions, aromatase staining was robust in developing sensory systems, including primary afferents of the olfactory, trigeminal, vestibulocochlear, and visual systems. To determine whether this aromatase is functional in these systems, i.e. converts testosterone to estradiol, the trigeminal nerve was dissected from the hindbrain of perinatal animals and studied for enzyme activity by the tritium release method. The dpm/mg protein/h tritium release in these tissues equalled that of hypothalamic or limbic controls, indicating that these sensory areas are sites of in-situ estradiol synthesis. Our data suggests that aromatase (estradiol)-dependent mechanisms may play a role in the differentiation and maturation of sensory pathways, which, in turn, may contribute to sex differences in the activity of these systems.
大鼠大脑中的性别差异部分取决于围产期特定发育阶段的雌激素暴露。雌激素的产生需要前体雄激素和神经元内芳香化酶的存在。为了研究大脑中雌激素形成和作用的部位,在胚胎第14天至出生后第20天期间,对大鼠大脑中芳香化酶进行了免疫细胞化学和生化定位。下丘脑、皮质和边缘区域存在芳香化酶免疫标记的神经元形态。令人惊讶的是,在以前未被怀疑的未成熟大脑的非边缘区域也观察到了芳香化酶免疫反应性。在这些区域中,芳香化酶染色在发育中的感觉系统中很强,包括嗅觉、三叉神经、前庭蜗神经和视觉系统的初级传入神经。为了确定这种芳香化酶在这些系统中是否有功能,即是否将睾酮转化为雌二醇,从围产期动物的后脑分离出三叉神经,并通过氚释放法研究其酶活性。这些组织中每毫克蛋白质每小时的氚释放量与下丘脑或边缘系统对照组相等,表明这些感觉区域是原位雌二醇合成的部位。我们的数据表明,芳香化酶(雌二醇)依赖性机制可能在感觉通路的分化和成熟中起作用,进而可能导致这些系统活动中的性别差异。