Institut de Ciències del Mar, Consejo Superior de Investigaciones Científicas (CSIC), Passeig Marítim, 37-49, 08003, Barcelona, Spain,
Fish Physiol Biochem. 2005 Apr;31(2-3):215-26. doi: 10.1007/s10695-006-0027-0.
Cytochrome P450 aromatase is the enzyme complex responsible for the synthesis of estrogens by the aromatization of androgens. In the vast majority of tetrapods examined so far, aromatase is the product of the Cyp19 gene, which exists as a single copy per haploid genome. In contrast, in teleosts there are two isoforms of the aromatase gene, Cyp19a and Cyp19b, which encode two structurally different proteins, P450aromA and P450aromB, respectively, with similar catalytic activities. The promoter region of both genes has been characterized in several teleost species and more than 20 different regulatory sites have been identified to date. These include response elements for members of the nuclear receptor superfamily, notably sex steroid receptors, and at least five transcription factors related to neurogenesis. This supports the idea that, besides other functions such as the control of reproduction, aromatase and therefore estrogens are actively involved in neurogenesis. Aromatase mRNA expression studies revealed that P450aromA and P450aromB are preferentially, but not exclusively, expressed in the gonads and brain, respectively. Other organs and tissues where aromatase is expressed, albeit at much lower levels include the pituitary, retina, anterior kidney, testis, liver and visceral fat, suggesting local actions of estrogens in several peripheral targets. Gene expression levels are usually matched by actual catalytic activity, with K (m) usually in the range 5-50 nM and V (max) in the order of a few pmol/mg protein/h. The current challenge is to understand the regulation of both aromatase genes, especially in the context of sex differentiation and as a response to environmental factors, including temperature, social interactions, and endocrine disruptors, which is briefly reviewed. It is also important to gain a better understanding of the specific functions of estrogen in different tissues and key developmental and reproductive events throughout the fish life.
细胞色素 P450 芳香酶是负责雄激素芳香化生成雌激素的酶复合物。到目前为止，在绝大多数研究过的四足动物中，芳香酶是 Cyp19 基因的产物，该基因在每个单倍体基因组中存在一个拷贝。相比之下，在硬骨鱼中，芳香酶基因有两个同工型，即 Cyp19a 和 Cyp19b，它们分别编码两种结构不同的蛋白质，即 P450aromA 和 P450aromB，具有相似的催化活性。这两个基因的启动子区域已在多种硬骨鱼物种中得到了描述，迄今为止已经鉴定出超过 20 个不同的调节位点。这些调节位点包括核受体超家族成员的反应元件，特别是性类固醇受体，以及至少五个与神经发生有关的转录因子。这支持了这样一种观点，即除了其他功能（如生殖控制）外，芳香酶（因此雌激素）也积极参与神经发生。芳香酶 mRNA 表达研究表明，P450aromA 和 P450aromB 分别优先但并非排他地在性腺和脑中表达。芳香酶在其他组织和器官中也有表达，尽管水平较低，包括垂体、视网膜、前肾、睾丸、肝脏和内脏脂肪，这表明雌激素在几个外周靶标中具有局部作用。基因表达水平通常与实际的催化活性相匹配，K(m) 值通常在 5-50 nM 范围内，V(max) 值在几个 pmol/mg 蛋白/h 左右。目前的挑战是了解这两个芳香酶基因的调节，特别是在性别分化方面，以及对环境因素的反应，包括温度、社会互动和内分泌干扰物，本文对此进行了简要综述。了解雌激素在不同组织中的特定功能以及鱼类生命周期中关键的发育和生殖事件也很重要。
