Identification and Characterization of the Androgen Receptor From the American Alligator, Alligator mississippiensis.
Identification and Characterization of the Androgen Receptor From the American Alligator, Alligator mississippiensis.
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DOI：
10.1210/en.2015-1037
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发表时间：
2015-05
期刊：
影响因子：
4.8
通讯作者：
S. Miyagawa;R. Yatsu;S. Kohno;Brenna M. Doheny;Y. Ogino;H. Ishibashi;Y. Katsu;Y. Ohta;L. Guillette-L
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文献类型：
--
作者：
S. Miyagawa;R. Yatsu;S. Kohno;Brenna M. Doheny;Y. Ogino;H. Ishibashi;Y. Katsu;Y. Ohta;L. Guillette-L
雄激素在脊椎动物的整个生命周期中对发育、生殖和健康至关重要，特别是在雄性性特征的启动和维持期间。雄激素信号传导由雄激素受体（AR）介导，雄激素受体是类固醇核受体超家族的成员。越来越多的证据表明，环境因素，如外源激素或污染物，模仿激素，可以破坏内分泌信号和功能。美洲短吻鳄（Alligator mississippiensis）是一种卵生、长寿的动物，具有环境依赖性的性别决定特性，是生态学研究的一个独特模式动物。来自受污染环境的短吻鳄表现出生殖成功率低，睾丸和阴茎在新生儿和青少年，都与雄激素信号转导的形态学障碍，因此，假设的改变是与破坏雄激素信号转导。然而，由于缺乏关于鳄鱼AR基因的信息，这一研究受到了限制。在这里，我们分离出A mississippiensis AR同源物（AmAR），并使用反式激活试验评估受体-激素/化学相互作用。我们发现，AmAR对所有天然雄激素都有反应，它们的作用可被抗雄激素（如氟啶虫胺、p，p '-二氯二苯基二氯乙烯和乙烯唑啉）共同处理所抑制。有趣的是，我们从鳄鱼cDNA中发现了一种剪接形式的AR，它在配体结合域中缺少7个氨基酸，对雄激素没有反应。最后，我们有一个可能的显性负功能的剪接形式的AR对雄激素诱导的AmAR的初步数据。
Androgens are essential for the development, reproduction, and health throughout the life span of vertebrates, particularly during the initiation and maintenance of male sexual characteristics. Androgen signaling is mediated by the androgen receptor (AR), a member of the steroid nuclear receptor superfamily. Mounting evidence suggests that environmental factors, such as exogenous hormones or contaminants that mimic hormones, can disrupt endocrine signaling and function. The American alligator (Alligator mississippiensis), a unique model for ecological research in that it exhibits environment-dependent sex determination, is oviparous and long lived. Alligators from a contaminated environment exhibit low reproductive success and morphological disorders of the testis and phallus in neonates and juveniles, both associated with androgen signaling; thus, the alterations are hypothesized to be related to disrupted androgen signaling. However, this line of research has been limited because of a lack of information on the alligator AR gene. Here, we isolated A mississippiensis AR homologs (AmAR) and evaluated receptor-hormone/chemical interactions using a transactivation assay. We showed that AmAR responded to all natural androgens and their effects were inhibited by cotreatment with antiandrogens, such as flutamide, p,p'-dichlorodiphenyldichloroethylene, and vinclozolin. Intriguingly, we found a spliced form of the AR from alligator cDNA, which lacks seven amino acids within the ligand-binding domain that shows no response to androgens. Finally, we have initial data on a possible dominant-negative function of the spliced form of the AR against androgen-induced AmAR.