Coumailleau P, Kah O
Neuroendocrine Effects of Endocrine Disruptors, IRSET, INSERM U1085, SFR Biosit, Université de Rennes 1, Rennes, France.
J Neuroendocrinol. 2014 Apr;26(4):226-36. doi: 10.1111/jne.12142.
Cytochrome P450 aromatase (P450arom; aromatase) is a microsomal enzyme involved in the production of endogeneous sex steroids by converting testosterone into oestradiol. Aromatase is the product of the cyp19a1 gene and plays a crucial role in the sexual differentiation of the brain and in the regulation of reproductive functions. In the brain of mammals and birds, expression of cyp19a1 has been demonstrated in neuronal populations of the telencephalon and diencephalon. By contrast, a wealth of evidence established that, in teleost fishes, aromatase expression in the brain is restricted to radial glial cells. The present study investigated the precise neuroanatomical distribution of cyp19a1 mRNA during brain development in Xenopus laevis (late embryonic to juvenile stages). For this purpose, we used in situ hybridisation alone or combined with the detection of a proliferative (proliferating cell nuclear antigen), glial (brain lipid binding protein, Vimentin) or neuronal (acetylated tubulin; HuC/D; NeuroβTubulin) markers. We provide evidence that cyp19a1 expression in the brain is initiated from the very early larval stage and remains strongly detected until the juvenile and adult stages. At all stages analysed, we found the highest expression of cyp19a1 in the preoptic area and the hypothalamus compared to the rest of the brain. In these two brain regions, cyp19a1-positive cells were never detected in the ventricular layers. Indeed, no co-labelling could be observed with radial glial (brain lipid binding protein, Vimentin) or dividing progenitors (proliferating cell nuclear antigen) markers. By contrast, cyp19a1-positive cells perfectly matched with the distribution of post-mitotic neurones as shown by the use of specific markers (HuC/D, acetylated tubulin and NeuroβTubulin). These data suggest that, similar to that found in other tetrapods, aromatase in the brain of amphibians is found in post-mitotic neurones and not in radial glia as reported in teleosts.
细胞色素P450芳香化酶(P450arom;芳香化酶)是一种微粒体酶,通过将睾酮转化为雌二醇参与内源性性类固醇的产生。芳香化酶是cyp19a1基因的产物,在大脑的性别分化和生殖功能调节中起关键作用。在哺乳动物和鸟类的大脑中,已证实在端脑和间脑的神经元群体中有cyp19a1的表达。相比之下,大量证据表明,在硬骨鱼类中,大脑中的芳香化酶表达仅限于放射状胶质细胞。本研究调查了非洲爪蟾(胚胎后期至幼体阶段)大脑发育过程中cyp19a1 mRNA的精确神经解剖分布。为此,我们单独使用原位杂交,或结合检测增殖(增殖细胞核抗原)、胶质(脑脂质结合蛋白、波形蛋白)或神经元(乙酰化微管蛋白;HuC/D;神经β微管蛋白)标记物。我们提供的证据表明,大脑中cyp19a1的表达从幼虫早期就开始了,并且在幼体和成年阶段一直能强烈检测到。在所有分析阶段,我们发现与大脑其他部位相比,视前区和下丘脑的cyp19a1表达最高。在这两个脑区,从未在室管膜层检测到cyp19a1阳性细胞。事实上,未观察到与放射状胶质(脑脂质结合蛋白、波形蛋白)或分裂祖细胞(增殖细胞核抗原)标记物的共标记。相比之下,如使用特异性标记物(HuC/D、乙酰化微管蛋白和神经β微管蛋白)所示,cyp19a1阳性细胞与有丝分裂后神经元的分布完全匹配。这些数据表明,与其他四足动物一样,两栖动物大脑中的芳香化酶存在于有丝分裂后神经元中,而不像硬骨鱼类那样存在于放射状胶质细胞中。