Induced synthesis of P450 aromatase and 17β-estradiol by D-aspartate in frog brain
Induced synthesis of P450 aromatase and 17β-estradiol by D-aspartate in frog brain
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DOI：
10.1242/jeb.073296
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发表时间：
2012-10-01
影响因子：
2.8
通讯作者：
Di Fiore, Maria Maddalena
中科院分区：
文献类型：
--
作者：
Burrone, Lavinia;Santillo, Alessandra;Di Fiore, Maria Maddalena
d -天冬氨酸是一种内源性氨基酸，存在于各种动物门的内分泌腺和神经系统中。我们之前的研究已经提供了证据，证明d -天冬氨酸在性腺诱导雌二醇合成中起作用。最近，我们也证明了d -天冬氨酸在青蛙睾丸中诱导P450芳香化酶mRNA的表达。P450芳香化酶是雌激素合成途径中的关键酶，可以不可逆地将睾酮转化为17 -雌二醇。在这项研究中，我们首先研究了P450芳香化酶在P. esculentus大脑中的免疫定位，这在两栖动物中从未被描述过。因此，为了验证d -天冬氨酸介导青蛙大脑中P450芳香化酶的局部合成的假设，我们给雄性青蛙体内注射d -天冬氨酸，然后评估大脑芳香化酶的表达、性激素水平和性激素受体的表达。我们发现d -天冬氨酸通过CREB途径增强脑芳香酶（mRNA和蛋白）的表达。然后，P450芳香化酶诱导睾丸激素产生17 -雌二醇，其受体随之增加。因此，调节d -天冬氨酸介导的P450芳香化酶表达可能是调控生殖轴神经内分泌调节的重要步骤。因此，我们发现青蛙大脑中P450芳香化酶免疫反应性的位点与已知参与神经类固醇合成的区域相对应。
D-Aspartic acid is an endogenous amino acid occurring in the endocrine glands as well as in the nervous system of various animal phyla. Our previous studies have provided evidence that D-aspartate plays a role in the induction of estradiol synthesis in gonads. Recently, we have also demonstrated that D-aspartic acid induces P450 aromatase mRNA expression in the frog (Pelophylax esculentus) testis. P450 aromatase is the key enzyme in the estrogen synthetic pathway and irreversibly converts testosterone into 17 beta-estradiol. In this study, we firstly investigated the immunolocalisation of P450 aromatase in the brain of P. esculentus, which has never previously been described in amphibians. Therefore, to test the hypothesis that D-aspartate mediates a local synthesis of P450 aromatase in the frog brain, we administered D-aspartate in vivo to male frogs and then assessed brain aromatase expression, sex hormone levels and sex hormone receptor expression. We found that D-aspartate enhances brain aromatase expression (mRNA and protein) through the CREB pathway. Then, P450 aromatase induces 17 beta-estradiol production from testosterone, with a consequent increase of its receptor. Therefore, the regulation of D-aspartate-mediated P450 aromatase expression could be an important step in the control of neuroendocrine regulation of the reproductive axis. Accordingly, we found that the sites of P450 aromatase immunoreactivity in the frog brain correspond to the areas known to be involved in neurosteroid synthesis.