雌激素受体(ER)被认为是所有类固醇受体的祖先,并且存在于迄今为止研究的大多数lophrochozoans中,包括软体动物,环节动物,和轮虫。许多研究已经调查了无脊椎动物中雌激素受体的功能作用,虽然大多数是软体动物,受体是组成型活性的。体外实验为环节动物中配体激活的雌激素受体提供了证据,提出了有关雌激素信号在lophrochozoan谱系中的作用的重要问题。这里,我们回顾了雌二醇受体信号传导的一致和不一致的证据,专注于环节动物和轮虫。我们探索雌激素的从头合成,雌激素受体的进化和表达,以及对无照虫门和轮虫中雌激素受体激活的生理反应。缺少关键数据来确定非软体动物中雌二醇的从头生物合成是否可能。例如,存在CYP11基因的直系同源物,但是缺乏底物转化和测量组织产物的确认。缺乏CYP17和CYP19的直系同源物,然而,已经测量了组织中的中间体或产物(例如雌二醇)。雌激素受体存在于多个物种中,对于有限的数量,体外数据显示雌二醇的激动剂结合和/或转录激活。lophrochozoanER的表达模式表明发育,生殖,和消化作用,但高度依赖于物种。E2暴露表明lophrochozoanER可能在繁殖中起作用,但尚未建立强剂量反应关系。因此,我们预计大多数lophrochozoan物种,在可能的桔梗之外,但他们的生理作用仍然难以捉摸。挖掘负责类固醇生成的直系同源基因家族的基因组,结合对类固醇途径的体外和体内研究,需要更好地评估lophrochozoans是否能够生物合成雌二醇。一个主要的挑战是,许多数据被划分为物种多样性。我们建议多毛菌Capitellateleta或Platynerisdumerilii,和轮虫Brachionusmanjavacas可能是研究雌激素受体信号的重要物种选择,因为现有的基因组数据,建立实验室培养技术,和基因敲除潜力。
Estrogen receptors (ERs) are thought to be the ancestor of all steroid receptors and are present in most lophotrochozoans studied to date, including molluscs, annelids, and rotifers. A number of studies have investigated the functional role of estrogen receptors in invertebrate species, although most are in molluscs, where the receptor is constitutively active. In vitro experiments provided evidence for ligand-activated estrogen receptors in annelids, raising important questions about the role of estrogen signalling in lophotrochozoan lineages. Here, we review the concordant and discordant evidence of estradiol receptor signalling in lophotrochozoans, with a focus on annelids and rotifers. We explore the de novo synthesis of estrogens, the evolution and expression of estrogen receptors, and physiological responses to activation of estrogen receptors in the lophotrochozoan phyla Annelida and Rotifera. Key data are missing to determine if de novo biosynthesis of estradiol in non-molluscan lophotrochozoans is likely. For example, an ortholog for the CYP11 gene is present, but confirmation of substrate conversion and measured tissue products is lacking. Orthologs CYP17 and CYP19 are lacking, yet intermediates or products (e.g. estradiol) in tissues have been measured. Estrogen receptors are present in multiple species, and for a limited number, in vitro data show agonist binding of estradiol and/or transcriptional activation. The expression patterns of the lophotrochozoan ERs suggest developmental, reproductive, and digestive roles but are highly species dependent. E2 exposures suggest that lophotrochozoan ERs may play a role in reproduction, but no strong dose-response relationship has been established. Therefore, we expect most lophotrochozoan species, outside of perhaps platyhelminths, to have an ER but their physiological role remains elusive. Mining genomes for orthologs gene families responsible for steroidogenesis, coupled with in vitro and in vivo studies of the steroid pathway are needed to better assess whether lophotrochozoans are capable of estradiol biosynthesis. One major challenge is that much of the data are divided across a diversity of species. We propose that the polychaetes Capitella teleta or Platyneris dumerilii, and
rotifer Brachionus manjavacas may be strong species choices for studies of estrogen receptor signalling, because of available genomic data, established laboratory culture techniques, and gene knockout potential.