Department of Endocrinology, Medical Centre for Postgraduate Education, Warszawa, Poland.
Endokrynol Pol. 2010 Jan-Feb;61(1):126-34.
Aromatase is a member of the cytochrome P450 superfamily that catalyzes the conversion of androgens (C(19)), namely testosterone and androstenedione, into oestrogens (C(18)), oestradiol, and oestrone, respectively. The enzyme is active in various tissues in both females and males, thus oestrogens are produced not only in gonads but also in extra-gonadal localizations such as brain, adipose tissue, breast, skin, and bone. Aromatase gene CYP19A1 located on chromosome 15 comprises nine coding exons and a number of alternative non-coding first exons that regulate tissue-specific expression. Studies on local regulation of aromatase expression and activity are important for understanding processes such as growth of oestrogen-dependent breast cancer. Rare clinical conditions of aromatase deficiency and excess have revealed some new and unexpected oestrogen functions in metabolism and bone health in both women and men. They were further studied using transgenic animal models such as aromatase knockout mice (ArKO) or (AROM+) mice overexpressing human aromatase. Research on aromatase was important for its practical outcome as it contributed to the development of aromatase inhibitors (AIs), an effective and safe group of drugs for the first-line endocrine therapy of breast cancer. Further studies are needed to establish AIs application in other oestrogen-dependent conditions, to overcome the resistance in breast cancer patients, and to develop tissue-specific selective inhibitors. (Pol J Endocrinol 2010; 61 (1): 126-134).
芳香酶是细胞色素 P450 超家族的一员，它催化雄激素（C(19)），即睾酮和雄烯二酮，分别转化为雌激素（C(18)），雌二醇和雌酮。该酶在女性和男性的各种组织中均具有活性，因此雌激素不仅在性腺中产生，而且在脑、脂肪组织、乳房、皮肤和骨骼等性腺外组织中产生。位于 15 号染色体上的芳香酶基因 CYP19A1 由九个编码外显子和一些调节组织特异性表达的替代非编码第一外显子组成。芳香酶表达和活性的局部调节研究对于理解雌激素依赖性乳腺癌的生长等过程非常重要。芳香酶缺乏和过量的罕见临床情况揭示了雌激素在女性和男性的代谢和骨骼健康中的一些新的、意想不到的功能。使用芳香酶敲除小鼠（ArKO）或过表达人芳香酶的（AROM+）小鼠等转基因动物模型进一步研究了这些功能。芳香酶的研究对于其实际结果很重要，因为它有助于开发芳香酶抑制剂（AIs），这是一种用于乳腺癌一线内分泌治疗的有效且安全的药物。需要进一步研究以确定 AIs 在其他雌激素依赖性疾病中的应用，以克服乳腺癌患者的耐药性，并开发组织特异性选择性抑制剂。（波兰内分泌学会杂志 2010 年；61 (1): 126-134）。
