Rissman E F, Harada N, Roselli C E
Department of Biology, University of Virginia, Charlottesville 22903, USA.
J Neuroendocrinol. 1996 Mar;8(3):199-210. doi: 10.1046/j.1365-2826.1996.04505.x.
Aromatase enzyme is essential for the expression of normal sexual behavior in many mammals and birds. Here we report that vorozole (R83842), a non-steroidal aromatase inhibitor, blocks sexual behavior in the female musk shrew. In addition, vorozole treatment lowers aromatase activity in male and female preoptic area, and reduces plasma estradiol concentrations in females. Our findings confirm and extend results demonstrated in other species, conducted with the active enantiomer (R83842), or the racemic mixture (R76713, racemic vorozole). We also report that vorozole treatment affects the immunocytochemical distribution of aromatase immunoreactivity (AROM-ir) in musk shrew brain. The histological identification of neurons that contain this enzyme has been difficult in mammals. Several aromatase enzyme antisera have been developed and used in brain, and each gives a different pattern of immunoreactivity. Moreover, despite the fact that aromatase activity is very high in the bed nucleus of the stria terminalis, several amygdala nuclei, the preoptic area and hypothalamus, AROM-ir in these regions has been very limited. The distribution of AROM-ir in female musk shew brain tissues is modified by treatment with vorozole prior to sacrifice. Female musk shrew brains contain aromatase immunoreactive cell bodies, as reported previously, in the central amygdala, lateral septum and to a limited extent in the bed nucleus of the stria terminalis (BST). Brains of females treated with vorozole show additional immunoreactivity in the preoptic area, hypothalamus, and medial amygdala, and have a broad distribution of AROM-ir in several subdivisions of the BST. Several sexual dimorphisms are apparent in musk shrews brains after treatment with vorozole. We have quantified this sexual dimorphism in the medial preoptic area (MPO) by counting immunoreactive cells. In both the rostral and caudal portions of the MPO, female brains contain significantly fewer AROM-ir cell bodies than males. These data are in complete agreement with sex differences in biochemical analyses of aromatase activity in the MPO. At this time we do not know if these dimorphisms are the result of differences in circulating levels of steroids in males and females, and/or if the AROM-ir nuclei regulate sexually dimorphic behaviors.
芳香化酶对于许多哺乳动物和鸟类正常性行为的表达至关重要。在此我们报告，非甾体芳香化酶抑制剂伏罗唑（R83842）可阻断雌性麝鼩的性行为。此外，伏罗唑处理可降低雄性和雌性视前区的芳香化酶活性，并降低雌性的血浆雌二醇浓度。我们的研究结果证实并扩展了在其他物种中使用活性对映体（R83842）或外消旋混合物（R76713，消旋伏罗唑）所得到的结果。我们还报告，伏罗唑处理会影响麝鼩脑中芳香化酶免疫反应性（AROM-ir）的免疫细胞化学分布。在哺乳动物中，对含有这种酶的神经元进行组织学鉴定一直很困难。已经开发了几种芳香化酶抗血清并用于脑研究，每种抗血清都给出不同的免疫反应模式。此外，尽管终纹床核、几个杏仁核、视前区和下丘脑的芳香化酶活性非常高，但这些区域的AROM-ir一直非常有限。在处死前用伏罗唑处理可改变雌性麝鼩脑组织中AROM-ir的分布。如先前报道，雌性麝鼩脑在中央杏仁核、外侧隔核以及终纹床核（BST）中有一定程度的芳香化酶免疫反应性细胞体。用伏罗唑处理的雌性脑在视前区、下丘脑和内侧杏仁核显示出额外的免疫反应性，并且在BST的几个亚区中有广泛的AROM-ir分布。用伏罗唑处理后，麝鼩脑中出现了几种性二态性。我们通过计数免疫反应性细胞，对内侧视前区（MPO）的这种性二态性进行了量化。在MPO的吻侧和尾侧部分，雌性脑含有的AROM-ir细胞体明显少于雄性。这些数据与MPO中芳香化酶活性的生化分析中的性别差异完全一致。目前我们尚不知道这些二态性是否是雄性和雌性循环类固醇水平差异的结果，以及/或者AROM-ir核是否调节性二态性行为。
