Peterson R Scott, Yarram Lakshmi, Schlinger Barney A, Saldanha Colin J
Physiological Sciences, UCLA, Los Angeles, CA, USA.
Proc Biol Sci. 2005 Oct 7;272(1576):2089-96. doi: 10.1098/rspb.2005.3181.
Oestrogens organize and activate circuits within the vertebrate central nervous system. Oestrogen synthesis occurs via the expression of aromatase, a P450 enzyme detected in microsomes and more recently in pre-synaptic boutons. Synaptic aromatase has only been described in brain regions that express aromatase in many subcellular compartments, so its function remains poorly understood. To more thoroughly study the role of oestrogen synthesis at synaptic terminals, we examined the ultrastructural compartmentalization of aromatase in the zebra finch; a species in which high aromatase activity can be measured in brain areas that do not contain somal aromatase. Here, we report the presence of aromatase in pre-synaptic boutons in the hippocampus and the high vocal centre brain areas with low and undetectable somal aromatase, respectively, in addition to areas with abundant somal aromatase such as the preoptic area and caudomedial nidopallium. At these brain areas, males had more total synapses, more aromatase pre-synaptic boutons and importantly, the proportion of total synaptic profiles that expressed aromatase was significantly higher in males relative to females. Aromatase-positive pre-synaptic boutons were always observed innervating aromatase-negative post-synaptic elements. We conclude that oestrogen may be provided to discrete oestrogen-sensitive targets by synaptic aromatization. Further, some targets may be exposed to more oestrogen in males. The expression of aromatase in individual synapses of projection neurons represents a unique mechanism of neuroendocrine action. Neurons with steroidogenic capability may modulate distant targets with the specificity of axonal innervation.
雌激素在脊椎动物中枢神经系统中构建并激活神经回路。雌激素通过芳香化酶的表达进行合成,芳香化酶是一种在微粒体中被检测到、最近又在突触前终扣中被发现的细胞色素P450酶。突触芳香化酶仅在许多亚细胞区室中表达芳香化酶的脑区中被描述过,因此其功能仍知之甚少。为了更深入地研究突触终末雌激素合成的作用,我们研究了斑胸草雀中芳香化酶的超微结构分区;在这个物种中,可以在不含体细胞芳香化酶的脑区中检测到高芳香化酶活性。在这里,我们报告了在海马体和高发声中枢脑区的突触前终扣中存在芳香化酶,在这些脑区中,体细胞芳香化酶含量低或无法检测到,此外,在视前区和尾内侧巢皮质等体细胞芳香化酶丰富的区域也存在芳香化酶。在这些脑区,雄性的突触总数更多,芳香化酶突触前终扣更多,重要的是,雄性中表达芳香化酶的突触总数比例相对于雌性显著更高。总是观察到芳香化酶阳性的突触前终扣支配芳香化酶阴性的突触后元件。我们得出结论,雌激素可能通过突触芳香化作用提供给离散的雌激素敏感靶点。此外,一些靶点在雄性中可能会接触到更多的雌激素。投射神经元单个突触中芳香化酶的表达代表了一种独特的神经内分泌作用机制。具有类固醇生成能力的神经元可能通过轴突支配的特异性来调节远处的靶点。