Filby Amy L, Thorpe Karen L, Tyler Charles R
Environmental and Molecular Fish Biology Group, School of Biosciences, Hatherly Laboratories, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS, UK.
J Mol Endocrinol. 2006 Aug;37(1):121-34. doi: 10.1677/jme.1.01997.
Complex interrelationships in the signalling of oestrogenic effects mean that environmental oestrogens present in the aquatic environment have the potential to disrupt physiological function in fish in a more complex manner than portrayed in the present literature. Taking a broader approach to investigate the possible effect pathways and the likely consequences of environmental oestrogen exposure in fish, the effects of 17beta-oestradiol (E(2)) were studied on the expression of a suite of genes which interact to mediate growth, development and thyroid and interrenal function (growth hormone GH (gh), GH receptor (ghr ), insulin-like growth factor (IGF-I) (igf1), IGF-I receptor (igf1r ), thyroid hormone receptors-alpha (thra) and -beta (thrb) and glucocorticoid receptor (gr )) together with the expression analyses of sex-steroid receptors and ten other genes centrally involved in sexual development and reproduction in fathead minnow (fhm; Pimephales promelas). Exposure of adult fhm to 35 ng E(2)/l for 14 days induced classic oestrogen biomarker responses (hepatic oestrogen receptor 1 and plasma vitellogenin), and impacted on the reproductive axis, feminising "male" steroidogenic enzyme expression profiles and suppressing genes involved in testis differentiation. However, E(2) also triggered a cascade of responses for gh, ghr, igf1, igf1r, thra, thrb and gr in the pituitary, brain, liver, gonad and gill, with potential consequences for the functioning of many physiological processes, not just reproduction. Molecular responses to E(2) were complex, with most genes showing differential responses between tissues and sexes. For example, igf1 expression increased in brain but decreased in gill on exposure to E(2), and responded in an opposite way in males compared with females in liver, gonad and pituitary. These findings demonstrate the importance of developing a deeper understanding of the endocrine interactions for unravelling the mechanisms of environmental oestrogen action and predicting the likely health consequences.
雌激素效应信号传导中的复杂相互关系意味着，水生环境中存在的环境雌激素有可能以比现有文献所描述的更为复杂的方式扰乱鱼类的生理功能。为了更广泛地研究鱼类接触环境雌激素的可能作用途径及其可能产生的后果，研究了17β-雌二醇（E₂）对一组相互作用以调节生长、发育以及甲状腺和肾上腺功能的基因（生长激素GH（gh）、GH受体（ghr）、胰岛素样生长因子（IGF-I）（igf1）、IGF-I受体（igf1r）、甲状腺激素受体-α（thra）和-β（thrb）以及糖皮质激素受体（gr））表达的影响，同时还对黑头呆鱼（fhm；肥头鲤）中性别类固醇受体以及另外十个在性发育和繁殖中起核心作用的基因进行了表达分析。成年fhm暴露于35 ng E₂/升环境中14天，引发了典型的雌激素生物标志物反应（肝脏雌激素受体1和血浆卵黄蛋白原），并影响了生殖轴，使“雄性”类固醇生成酶表达谱出现雌性化，并抑制了参与睾丸分化的基因。然而，E₂还引发了垂体、脑、肝脏、性腺和鳃中gh、ghr、igf1、igf1r、thra、thrb和gr的一系列反应，这可能对许多生理过程的功能产生影响，而不仅仅是生殖功能。对E₂的分子反应很复杂，大多数基因在不同组织和性别之间表现出差异反应。例如，暴露于E₂时，igf1在脑中的表达增加，但在鳃中减少，并且在肝脏、性腺和垂体中，雄性与雌性的反应方式相反。这些发现表明，深入了解内分泌相互作用对于阐明环境雌激素作用机制以及预测可能的健康后果至关重要。
